The cells developing resistance to an applied drug may also present cross-resistance to other anticancer drugs which are not applied. In this study, the development of cross-resistance in paclitaxel (MCF-7/Pac), docetaxel (MCF-7/Doc), vincristine (MCF-7/Vinc) and doxorubicin (MCF-7/Dox) resistant MCF-7 cells to selective anticancer drugs, tamoxifen and all trans-retinoic acid (ATRA) were investigated. Combined antiproliferative effects of these drugs in different combinations were also evaluated by checkerboard combination assay. MCF-7/Pac and MCF-7/Doc cells developed cross-resistance to vincristine (13- and 12-folds, respectively) and tamoxifen (3- and 2-folds, respectively). MCF-7/Dox cells developed cross-resistance to paclitaxel (109-fold), docetaxel (10-fold), tamoxifen (2-fold) and ATRA (3-fold). MCF-7/Vinc cells developed cross-resistance to paclitaxel (48-fold), doxorubicin (6-fold) and tamoxifen (2-fold). Combinations of paclitaxel and docetaxel with doxorubicin exerted synergic anti proliferative effect. Tamoxifen had synergic effect with doxorubicin and vincristine. ATRA had indifferent effect with paclitaxel, docetaxel and doxorubicin where it had antagonistic effect with vincristine. The data presented here may provide an insight to assess response of breast tumors to anticancer drug combinations.