Amyloid deposits in primary cutaneous amyloidosis (PCA) may be initially derived from cytokeratin. possibly after keratinocyte death. However, the mechanism of keratinocyte death remains obscure. To investigate the potential role of apoptosis in the pathogenesis of PCA, a retrospective study was conducted on the skin tissues from 20 Chinese patients with PCA. We used a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) method for detecting the apoptotic cells. Immunohistochemical staining was performed to examine the expression of the B-cell leukemia/lymphoma-2 gene (bcl-2) and Fas. Apoptotic cells were shown in 11 of 20 cases (55%) by TUNEL. Histological sections showed that dyskeratotic cells and vacuolar alteration of the basal cells were more commonly observed in the TUNEL-positive group. In all cases of PCA, epidermal expression of bcl-2 was minimal, while expression of Fas was observed on keratinocytes in the basal to granular layers: however, these findings were not different from those in normal skin. Our results suggest that the keratinocyte destruction in PCA may occur as an initial result of apoptosis, which in turn leads to the amyloid formation.