Multicentric squamous cell carcinoma in situ was studied in 12 cats (eight castrated males and four spayed females). The neoplasms occurred in middle-aged to old (mean age = 12 years) mixed-breed cats with a variety of hair-coat colors. The lesions were found in haired pigmented regions of the skin, including the trunk, limbs, feet, head, and neck, and were unrelated to exposure to sunlight. Lesions occurred at multiple sites in nine cats and at solitary sites in three cats and were from 0.5 cm to 3.0 cm in diameter, irregular, slightly elevated, plaque-like or papillated, and partially alopecic. Histologically, the lesions consisted of sharply demarcated regions of neoplastic, keratinocytic infiltration of the epidermal and follicular infundibular epithelium. Neoplastic cells were confined to the epithelium without frank invasion of the dermis. Two histologic subclasses of multicentric squamous cell carcinoma in situ were identified, the irregular nonhyperkeratotic type and the verrucous hyperkeratotic type. Three cats also had invasive squamous cell carcinoma adjacent to lesions characteristic of multicentric squamous cell carcinoma in situ. Grossly, these were solitary 2.0-4.0 cm-diameter firm, crusted, crateriform cutaneous masses. During follow-up periods of 4 to 20 months (mean follow-up period = 11 months), neoplasms did not recur locally after surgical excision; however, similar lesions developed at new sites in four cats.(ABSTRACT TRUNCATED AT 250 WORDS)