Low molecular weight cytokeratin (LCK) and high molecular weight cytokeratin (HCK) were analyzed by immunohistochemistry using two monoclonal antibodies in 90 patients with operable invasive breast carcinoma (IBC). Fifty-nine (65.6%) of 90 tumors were LCK-positive, and 19 (21.1%) were HCK-positive. The incidence of LCK positivity was inversely correlated with nuclear or histological grade, however, the incidence of HCK positivity was positively correlated. The positive correlation of the incidence of LCK positivity with estrogen receptor (ER) status was observed, however, the inverse correlation was found between the incidence of HCK positivity and ER status. The mean of ER content (101.9 fmol/mg protein) in LCK-positive tumors was significantly higher than that (20.8 fmol/mg protein) in LCK-negative tumors. To the contrary, the mean of ER content (10.1 fmol/mg protein) in HCK-positive tumors was significantly lower than that (91.3 fmol/mg protein) in HCK-negative tumors. Overall survival (OS) and relapse-free survival (RFS) of patients with LCK-positive tumors tended to be better than those of patients with LCK-negative tumors. No difference was demonstrated between OS and RFS of patients with HCK-positive tumors and those of patients with HCK-negative tumors. LCK-positive IBC can be well differentiated and HCK-positive IBC poorly differentiated. The immunohistochemical analysis for LCK and HCK can be utilized to evaluate the differentiation of IBC. Furthermore, LCK immunoreactivity might be one of the prognostic factors of IBC, and HCK immunoreactivity could be useful for the histological diagnosis for carcinoma with metaplasia, such as squamous cell or spindle cell carcinoma.