Abstract: In the present study, the protein expression levels of Thymidylate Synthase (TS) and Thymidine Phosphorylase (TP) were determined in human breast cancer T47D cells and its derived TAM resistant subline (T47D/TAMR-6 cells). The resistant subline was established in vitro following stepwise increase in TAM concentration in the culture medium of parent cells. Immunocytochemical method was used to determine the expression of TS and TP enzymes in both parent and resistant cells. The slow growing T47D/TAMR-6 cells showed lower level of expression of both proteins compare to parent T47D cells. Expression of TS was also observed to be more than TP in both studied cell types. In conclusion, in patients with tumor immunophenotype similar to these two cell lines, the efficacy of 5-FU chemotherapy and its congeners will be expected to be different. This in turn would affect the disease prognosis and therapeutic predictions. Therefore, the outcome for 5-FU-containing chemotherapy regimens when applied after tumor progression on hormonal therapy is better to be weighed against the status of TS and TP protein levels.