Prurigo nodularis is a chronic disease with unknown aetiology. Biopsy specimens of 43 patients with prurigo nodularis were taken for histopathological and mycobacteriological analyses. By conventional histopathology, 25 (58 %) samples, and by immunostaining for S100 protein, 31 (72 %) samples had changes relevant to prurigo nodularis. Twelve (28 %) of the samples were positive for acid fast bacilli in tissue staining by Ziehl-Neelsen technique, including 4 of the 6 samples also positive for mycobacteria in cultivation. The results verified the usefulness of S100 staining in detection of neural hyperplasia in dermal nerves, a feature regarded as diagnostic for prurigo nodularis. They also indicated that atypical mycobacteria may be a contributing factor in prurigo nodularis.