diff --git a/keys.cc b/keys.cc
index f9d1d2308a..6077137592 100644
--- a/keys.cc
+++ b/keys.cc
@@ -38,12 +38,18 @@ partition_key_view::ring_order_tri_compare(const schema& s, partition_key_view k
 
 partition_key partition_key::from_nodetool_style_string(const schema_ptr s, const sstring& key) {
     std::vector<sstring> vec;
-    boost::split(vec, key, boost::is_any_of(":"));
+    if (s->partition_key_type()->types().size() == 1) {
+        // For a single column partition key. Don't try to split the key
+        // See #16596
+        vec.push_back(key);
+    } else {
+        boost::split(vec, key, boost::is_any_of(":"));
+        if (vec.size() != s->partition_key_type()->types().size()) {
+            throw std::invalid_argument(fmt::format("partition key '{}' has mismatch number of components: expected {}, got {}", key, s->partition_key_type()->types().size(), vec.size()));
+        }
+    }
 
     auto it = std::begin(vec);
-    if (vec.size() != s->partition_key_type()->types().size()) {
-        throw std::invalid_argument("partition key '" + key + "' has mismatch number of components");
-    }
     std::vector<bytes> r;
     r.reserve(vec.size());
     for (auto t : s->partition_key_type()->types()) {
diff --git a/test/boost/keys_test.cc b/test/boost/keys_test.cc
index a2ebfe0659..252349e52b 100644
--- a/test/boost/keys_test.cc
+++ b/test/boost/keys_test.cc
@@ -159,7 +159,7 @@ BOOST_AUTO_TEST_CASE(test_serialization) {
 }
 
 
-BOOST_AUTO_TEST_CASE(test_from_nodetool_style_string) {
+BOOST_AUTO_TEST_CASE(test_from_nodetool_style_string_single_partition_key) {
     auto s1 = schema_builder("", "")
             .with_column("c1", utf8_type, column_kind::partition_key)
             .with_column("c2", bytes_type, column_kind::clustering_key)
@@ -169,10 +169,15 @@ BOOST_AUTO_TEST_CASE(test_from_nodetool_style_string) {
 
     auto pk_value = bytes("value");
     partition_key key1(std::vector<bytes>({pk_value}));
-
     auto key2 = partition_key::from_nodetool_style_string(s1, "value");
     BOOST_REQUIRE(key1.equal(*s1, key2));
 
+    auto pk_with_col_value = bytes("val:ue");
+    partition_key key_with_col(std::vector<bytes>({pk_with_col_value}));
+    BOOST_REQUIRE(key_with_col.equal(*s1, partition_key::from_nodetool_style_string(s1, "val:ue")));
+}
+
+BOOST_AUTO_TEST_CASE(test_from_nodetool_style_string_composite_partition_key) {
     auto s2 = schema_builder("", "")
             .with_column("c1", utf8_type, column_kind::partition_key)
             .with_column("c2", utf8_type, column_kind::partition_key)
@@ -183,7 +188,9 @@ BOOST_AUTO_TEST_CASE(test_from_nodetool_style_string) {
     auto pk_value1 = bytes("value1");
     auto pk_value2 = bytes("value2");
     partition_key key3(std::vector<bytes>({pk_value1, pk_value2}));
-
     auto key4 = partition_key::from_nodetool_style_string(s2, "value1:value2");
-    BOOST_REQUIRE(key3.equal(*s1, key4));
+    BOOST_REQUIRE(key3.equal(*s2, key4));
+
+    BOOST_REQUIRE_THROW(partition_key::from_nodetool_style_string(s2, "value1:value2:extra"), std::invalid_argument);
+    BOOST_REQUIRE_THROW(partition_key::from_nodetool_style_string(s2, "value1"), std::invalid_argument);
 }
diff --git a/test/rest_api/test_storage_service.py b/test/rest_api/test_storage_service.py
index f73dc30bfc..7f29bf2348 100644
--- a/test/rest_api/test_storage_service.py
+++ b/test/rest_api/test_storage_service.py
@@ -629,6 +629,25 @@ def test_storage_service_get_natural_endpoints(cql, rest_api, tablets_enabled, s
 
             assert resp.json() == [rest_api.host]
 
+@pytest.mark.parametrize("tablets_enabled", ["true", "false"])
+def test_storage_service_get_natural_endpoints_compound_key(cql, rest_api, tablets_enabled, skip_without_tablets):
+    with new_test_keyspace(cql, f"WITH REPLICATION = {{ 'class' : 'NetworkTopologyStrategy', 'replication_factor' : 1 }} AND TABLETS = {{ 'enabled': {tablets_enabled} }}") as keyspace:
+        with new_test_table(cql, keyspace, 'p1 int, p2 text, c int, PRIMARY KEY ((p1, p2), c)') as t0:
+            table = t0.split(".")[1]
+            resp = rest_api.send("GET", f"storage_service/natural_endpoints/{keyspace}", params={"cf": table, "key": "1:value"})
+            resp.raise_for_status()
+            assert resp.json() == [rest_api.host]
+
+# Verify that a single-column partition key containing ':' is not split. Reproduces #16596
+@pytest.mark.parametrize("tablets_enabled", ["true", "false"])
+def test_storage_service_get_natural_endpoints_text_key_with_colon(cql, rest_api, tablets_enabled, skip_without_tablets):
+    with new_test_keyspace(cql, f"WITH REPLICATION = {{ 'class' : 'NetworkTopologyStrategy', 'replication_factor' : 1 }} AND TABLETS = {{ 'enabled': {tablets_enabled} }}") as keyspace:
+        with new_test_table(cql, keyspace, 'p text PRIMARY KEY') as t0:
+            table = t0.split(".")[1]
+            resp = rest_api.send("GET", f"storage_service/natural_endpoints/{keyspace}", params={"cf": table, "key": "value:123"})
+            resp.raise_for_status()
+            assert resp.json() == [rest_api.host]
+
 def test_range_to_endpoint_map_tablets_enabled_keyspace_param_only(cql,  rest_api, skip_without_tablets):
     with new_test_keyspace(cql, "WITH REPLICATION = { 'class' : 'NetworkTopologyStrategy', 'replication_factor' : 1 } AND TABLETS = { 'enabled': true }") as keyspace:
         with new_test_table(cql, keyspace, 'p int PRIMARY KEY') as table: