In [119]: common = df1.merge(df2,on=['col1','col2']) print(common) df1[(~df1.col1.isin(common.col1))&(~df1.col2.isin(common.col2))] col1 col2 0 1 10 1 2 11 2 3 12 Out[119]: col1 col2 3 4 13 4 5 14