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Superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis) are 2 types of nonmelanoma skin cancers (NMSCs) that are amenable to treatment with topical 5-fluorouracil, cryosurgery, or topical imiquimod, among other destructive and surgical modalities. There are few studies examining the effectiveness of combination therapy with 5% 5-fluorouracil and cryosurgery for the treatment of sBCC and SCCis.Our objective was to study the clinical cure rate achieved with the regimen of cryosurgery and a 3-week course of 5% 5-fluorouracil in the treatment of biopsy-proven sBCC and SCCis.A retrospective chart review of patients treated with cryosurgery and a 3-week course of 5% 5-fluorouracil was performed. Immunocompetent patients with biopsy-proven sBCC or SCCis who completed the treatment and attended a follow-up appointment at 6 months were included in the study.On clinical examination, 30 sBCC lesions of the 34 that were assessed and 31 SCCis lesions of the 33 that were assessed demonstrated no evidence of recurrence. The clinical cure rates were found to be 73% (sBCC) and 82% (SCCis), with the inclusion of patients that were lost to follow-up.This approach may represent a suitable option for select patients for the treatment of SCCis. Further studies with a longer follow-up duration, documentation of histologic cure, and tolerability of this regimen for SCCis are needed. The effectiveness of cryosurgery and 5-fluorouracil for sBCC requires further study.