Intratumoral granulomas and granulomas in lymph nodes draining breast carcinomas have been reported previously. However, in regions like Pakistan, where the incidence of tuberculosis (TB) is high, it is sometimes difficult to distinguish between TB and a non-specific granulomatous response especially if there is an association with focal necrosis. We present a series of cases of invasive breast carcinoma with an associated granulomatous reaction in lymph nodes with or without necrosis, which were further analyzed for a possible coexisting tuberculosis using special stains and PCR-based assays for the identification of Mycobacterium tuberculosis. Twenty-two cases were examined using ZN stain for AFB and PAS stain for fungal organisms. Nested PCR assays for M. tuberculosis DNA were performed on formalin-fixed, paraffin-embedded tissue. In all the cases, ZN stain for AFB and PAS stain for fungus were negative. M. tuberculosis DNA was detected in 11 (50%) out of the 22 cases. Six of 12 cases which had granulomas in association with necrosis were positive for MTB-DNA, while 5 of 10 cases without necrosis were also positive for MTB-DNA. It is concluded that the presence of granulomas with or without necrosis in association with malignancies should be further evaluated, particularly in regions with a high prevalence of tuberculosis, for the possibility of coexistent tuberculosis, as this may alter the postoperative management of the patient. PCR-based assays are recommended for the diagnosis of TB in cases where ZN is unhelpful for demonstrating AFB or no tissue is submitted for microbiological studies.