The expression of Cathepsin - D (Cath - D), c - erbB - 2 and EGFR in breast cancer and its correlation to lymphatic metastases were studied in 277 cases by imnnmohistochemical technique. Positive staining of Cath- D was detected in 107 cases (38.62%). Among those, 89 cases (83.17%)had docmnented metastases in the lymph nodes. One hundred and seventy cases ( 61.38% ) stained negative for Cath - D. Of which 64 cases (37.64 % ) had detectable lymphatic metastases. There is a significant difference in the rate of the lymphatic metastases between the Cath- D positive and Cath - D negative groups ( x² = 55.05 P < 0.0001). Fifty-six out of 107 Cath- D positive cases (52.23%) were c-erbB-2 positive as well. However, only 27 out of 170 Cath- D negative cases (15.88%) wene e-erbB-2 positive. The positive rate of c-erbB-2 in Cath - D positive group was significantly different from that of Cath - D negative group ( x² = 41.58 P<0.0001). Among those 107 Cath- D positive cases,49 cases (45.79%) were EGFR positive. Only 24 cases (14.12%) were EGFR positive among the 170 Cath - D negative cases. The positive rate of EGFR betwe~ these two groups was also significantly different ( x² = 33.95 P < 0.0001). An analysis of the three mentioned markers, the lymph node metastasis and hanor size suggests that Cath- D is the most valuable indicator for tmnor aggressiveness. Breast cancer cases with a positive Cath - D staining are more likely to have lymphatic metastases and a poor prognosis. Therefore, alternative therapeutic strategies and close follow ups are appropriate for these patients.