Pathologists are expected to accurately diagnose increasingly smaller breast carcinomas. Correct classification (ie, lobular vs ductal or in situ vs invasive) directly affects subsequent management, especially when the focus is near a surgical margin or present in a needle core biopsy and is further challenging if the lesion is morphologically ambiguous. We assessed the diagnostic utility of a multiplex, trichromogen immunostain of 3 commonly employed antibodies (CK7, p63, and E-cadherin) developed in our laboratory to evaluate these small lesions. Of the 147 specimens containing minimal (defined as ≤3 mm in size) invasive carcinoma, 81 also contained in situ carcinoma. In each case, the Minimal Carcinoma Triple Stain was prepared with a parallel H&E-stained slide. Observations of staining characteristics in the focus of interest were recorded. The Minimal Carcinoma Triple Stain was diagnostically useful in all but 1 case. In a case of invasive lobular carcinoma in an excisional biopsy, the Minimal Carcinoma Triple Stain stained only the surrounding breast tissue (appropriately) and not the focus of interest. Also, a subset of 29 of 81 excisional biopsies had minimal invasive carcinoma located 2 mm or less from the inked surgical margin, in which in all cases the Minimal Carcinoma Triple Stain was fully interpretable despite morphologic distortion due to concomitant cautery artifact and tissue disruption in some cases. The Minimal Carcinoma Triple Stain offers an accurate and tissue-conserving method to diagnose small, morphologically problematic foci of breast carcinoma while ideally leaving more tissue for additional adjunctive studies.