Background: In routine dermatopathology there is growing demand for a simple, fast, cost-effective, and highly sensitive screening tool for the detection of microorganisms. Objective: Our purpose was to determine whether immunostaining with polyclonal anti–Mycobacterium bovis (BCG), which is known for its interspecies cross-reactivity, is a suitable screening method for many common microorganisms in dermatopathologic specimens. Methods: A total of 254 formalin-fixed, paraffin-embedded skin specimens of viral, protozoal, fungal, and bacterial infections were stained with appropriate histochemical stains and with anti-BCG. Results: Anti-BCG labeled bacteria and fungi with high sensitivity and minimal background staining, but did not react with spirochetes, viruses, or protozoa (Leishmania). The quality and sensitivity of anti-BCG staining were superior to conventional histochemical stains. Conclusion: Because of its cross-reactivity with many bacteria and fungi as well as its high sensitivity and minimal background staining, the anti-BCG immunostain is a promising screening tool for the detection of the most common bacterial and fungal microorganisms in paraffin-embedded skin specimens. (J Am Acad Dermatol 1998;38:56-60.)