diff --git a/asv_bench/benchmarks/algos/isin.py b/asv_bench/benchmarks/algos/isin.py
index 296101c9f9800..427af9307f2c9 100644
--- a/asv_bench/benchmarks/algos/isin.py
+++ b/asv_bench/benchmarks/algos/isin.py
@@ -325,3 +325,13 @@ def setup(self, dtype, series_type):
 
     def time_isin(self, dtypes, series_type):
         self.series.isin(self.values)
+
+
+class IsInWithLongTupples:
+    def setup(self):
+        t = tuple(range(1000))
+        self.series = Series([t] * 1000)
+        self.values = [t]
+
+    def time_isin(self):
+        self.series.isin(self.values)
diff --git a/pandas/_libs/src/klib/khash_python.h b/pandas/_libs/src/klib/khash_python.h
index c8e1ca5ebb4d3..4d7875be7e5fd 100644
--- a/pandas/_libs/src/klib/khash_python.h
+++ b/pandas/_libs/src/klib/khash_python.h
@@ -226,6 +226,9 @@ int PANDAS_INLINE tupleobject_cmp(PyTupleObject* a, PyTupleObject* b){
 
 
 int PANDAS_INLINE pyobject_cmp(PyObject* a, PyObject* b) {
+    if (a == b) {
+        return 1;
+    }
     if (Py_TYPE(a) == Py_TYPE(b)) {
         // special handling for some built-in types which could have NaNs
         // as we would like to have them equivalent, but the usual