diff --git a/doc/source/whatsnew/v0.18.0.txt b/doc/source/whatsnew/v0.18.0.txt
index 193d8f83ded79..292444a2bbacc 100644
--- a/doc/source/whatsnew/v0.18.0.txt
+++ b/doc/source/whatsnew/v0.18.0.txt
@@ -203,6 +203,8 @@ In addition, ``.round()``, ``.floor()`` and ``.ceil()`` will be available thru t
 
 .. _whatsnew_0180.api:
 
+- ``pandas.merge()`` and ``DataFrame.merge()`` will show a specific error message when trying to merge with an object that is not of type ``DataFrame`` or a subclass (:issue:`12081`)
+
 .. _whatsnew_0180.api_breaking:
 
 Backwards incompatible API changes
diff --git a/pandas/tools/merge.py b/pandas/tools/merge.py
index 6ea217c4a72a7..60dda9183e7d5 100644
--- a/pandas/tools/merge.py
+++ b/pandas/tools/merge.py
@@ -184,6 +184,13 @@ def __init__(self, left, right, how='inner', on=None,
             raise ValueError(
                 'indicator option can only accept boolean or string arguments')
 
+        if not isinstance(left, DataFrame):
+            raise ValueError(
+                'can not merge DataFrame with instance of type {0}'.format(type(left)))
+        if not isinstance(right, DataFrame):
+            raise ValueError(
+                'can not merge DataFrame with instance of type {0}'.format(type(right)))
+
         # note this function has side effects
         (self.left_join_keys,
          self.right_join_keys,
diff --git a/pandas/tools/tests/test_merge.py b/pandas/tools/tests/test_merge.py
index 9e64e0eeb2792..8be15b212085a 100644
--- a/pandas/tools/tests/test_merge.py
+++ b/pandas/tools/tests/test_merge.py
@@ -261,6 +261,18 @@ def test_join_on_fails_with_different_column_counts(self):
                             index=tm.makeCustomIndex(10, 2))
             merge(df, df2, right_on='a', left_on=['a', 'b'])
 
+
+    def test_join_on_fails_with_wrong_object_type(self):
+        # GH12081
+        wrongly_typed = [Series([0, 1]), 2, 'str', None, np.ndarray([0, 1])]
+        df = DataFrame({'a': [1, 1]})
+
+        for obj in wrongly_typed:
+            with tm.assertRaisesRegexp(ValueError, str(type(obj))):
+                merge(obj, df, left_on='a', right_on='a')
+            with tm.assertRaisesRegexp(ValueError, str(type(obj))):
+                merge(df, obj, left_on='a', right_on='a')
+
     def test_join_on_pass_vector(self):
         expected = self.target.join(self.source, on='C')
         del expected['C']