BUG: setitem raising for rhs with midx columns and tuple indexer

doc/source/whatsnew/v2.0.0.rst

@@ -216,6 +216,7 @@ Interval
 Indexing
 ^^^^^^^^
 - Bug in :meth:`DataFrame.reindex` filling with wrong values when indexing columns and index for ``uint`` dtypes (:issue:`48184`)
+- Bug in :meth:`DataFrame.__setitem__` raising ``ValueError`` when right hand side is :class:`DataFrame` with :class:`MultiIndex` columns (:issue:`49121`)
 - Bug in :meth:`DataFrame.reindex` casting dtype to ``object`` when :class:`DataFrame` has single extension array column when re-indexing ``columns`` and ``index`` (:issue:`48190`)
 - Bug in :func:`~DataFrame.describe` when formatting percentiles in the resulting index showed more decimals than needed (:issue:`46362`)
 

pandas/core/frame.py

@@ -4110,7 +4110,7 @@ def _set_item_frame_value(self, key, value: DataFrame) -> None:
         if key in self.columns:
             loc = self.columns.get_loc(key)
             cols = self.columns[loc]
-            len_cols = 1 if is_scalar(cols) else len(cols)
+            len_cols = 1 if is_scalar(cols) or isinstance(cols, tuple) else len(cols)
             if len_cols != len(value.columns):
                 raise ValueError("Columns must be same length as key")
 

pandas/tests/frame/indexing/test_setitem.py

@@ -748,6 +748,14 @@ def test_setitem_frame_overwrite_with_ea_dtype(self, any_numeric_ea_dtype):
         )
         tm.assert_frame_equal(df, expected)
 
+    def test_setitem_frame_midx_columns(self):
+        # GH#49121
+        df = DataFrame({("a", "b"): [10]})
+        expected = df.copy()
+        col_name = ("a", "b")
+        df[col_name] = df[[col_name]]
+        tm.assert_frame_equal(df, expected)
+
 
 class TestSetitemTZAwareValues:
     @pytest.fixture