We have studied the clinical and histopathologic features of 44 biopsy specimens of large-cell acanthoma (LCA) from 35 patients. There were 19 women and 16 men, 34-88 years of age (mean 75). The lesions were mainly located on the head and extremities, usually solitary, less than or equal to 10 mm in diameter, and of greater than or equal to 1 year's duration. However, there were also cases of multiple and larger lesions, and those of shorter duration. The most frequently offered clinical diagnoses were seborrheic keratosis, Bowen's disease, and LCA; two cases had the clinical features of stucco keratosis. Histologically, 41 of the specimens could be classified into three patterns: 16 lesions showed a basic pattern (mild to moderate acanthosis, hyperkeratosis, large cytoplasms and nuclei, hyperpigmentation, and bulbous rete ridges); 12 specimens showed a verrucous pattern (papillomatosis and hyperkeratosis resembling church spires); and 13 lesions exhibited a flat-hyperkeratotic pattern (compact hyperkeratosis arranged in horizontal layers of corneocytes lying on a band-like acanthotic stratum malpighii that lacks both rete ridges and papillae). Some cases exhibiting this latter pattern showed focal bowenoid changes. Some mixed and intermediate lesions demonstrated the existence of a spectrum. We have concluded that LCA is a distinctive condition with various stages of development and is probably related to stucco keratosis. It can clearly be separated histologically from solar lentigo and from solar keratosis. As other epidermal tumors, LCA can sometimes exhibit features of Bowen's disease.