In our previous study, oral adjuvant combination chemotherapy of 5-fluorouracil, cyclophosphamide, mitomycin C, and predonisolone (FEMP) after curative resection of operable breast cancer with vascular invasion in the tumor and/or in the metastatic lymph node was found to be more effective than one course of mitomycin C or cyclic course of mitomycin C. In the present study, we have assessed the efficacy of protein-bound polysaccharide (PSK) or levamisole (LMS) in addition to FEMP. Between January 1980 and December 1990, 227 operable breast cancer patients with vascular invasion in the tumor and/or in the metastatic lymph node were randomized into FEMP, FEMP + LMS, or FEMP + PSK. The risk ratio was lower in the FEMP + PSK group compared to the FEMP group. In disease-free survival or overall survival, there was no significant difference between the three groups, however, the survival curve of the FEMP + PSK group tended to be better than that of the FEMP group(logrank, P = 0.0706; generalized Wilcoxon, P = 0.0739). Side effects were observed at a low incidence, but they were mild and tolerable. Immunochemotherapy using PSK improved the prognosis of patients with operable breast cancer with vascular invasion.