Cathepsin (Cat) L is an important lysosomal proteinase involved in a variety of cellular functions including intracellular protein turnover, epidermal homeostasis and hair development. Hurpin (serpinB13) is a cross-class specific serine protease inhibitor of Cat L. We have analysed the expression and localization of Cat L and hurpin in various inflammatory and neoplastic diseases by immunohistochemistry. Whereas Cat L expression in normal skin was below detection limit, immunoreactivity was detected in chronic inflammatory dermatoses. The highest expression of Cat L was found in psoriasis, atopic eczema and squamous cell carcinoma (SCC) samples. Samples of Lupus erythematosus, folliculitis, acne inversa, chronic leg ulcers and pyoderma gangrenosum demonstrated similar but lower expression for Cat L. In malignant cells of SCC, basal cell carcinoma and malignant melanoma, characteristic staining patterns were observed for Cat L, with more abundant expression at the periphery of the tumor. Expanding our previous work, we found that the expression of hurpin was confined mainly to the basal layer in normal skin samples, whereas hurpin was overexpressed and redistributed in diseased skin. The localization of hurpin in dermatoses and neoplasias differed from that in normal skin in that the highest expression was found in the outermost layers of the granular and upper spinous layers. Similarly to Cat L, the highest expression for hurpin was found in psoriasis and SCC. The results presented here summarize for the first time the expression of the protease Cat L and its inhibitor hurpin in a broad spectrum of skin diseases.