Forty biopsies of granulomatous dermatoses, 12 of which were tuberculoid leprosy (TL), were studied for patterns of nerve twig distribution using an immunoperoxidase technique for S-100 protein. Four distinct patterns of nerve twigs were identified: 1) within granulomas, 2) between granulomas, 3) within and between granulomas, and 4) undetectable nerve twigs in an adequate biopsy. Pattern 4 was seen exclusively in TL (p < 0.05). The other patterns occurred in nonleprosy dermatoses as well, suggesting that pattern 4 is the best indicator toward a diagnosis of TL. The granules of mycetoma and Mycobacterium leprae also stained positively with the S-100 stain.