Axillary giant basal cell carcinoma is extremely rare and remains challenging for physicians. The few reported cases have a relatively short-term follow-up, and none were treated with an oral hedgehog pathway inhibitor. Herein, we report the case of a 71-year-old man with a giant basal cell carcinoma in the axilla. The primary treatment instituted was surgical excision and adjuvant radiotherapy. The tumor recurred 4.5 years later, and 6-month treatment with vismodegib, a hedgehog pathway inhibitor, was effective. The disease progression re-occurred 1.5 years after discontinuing vismodegib. Palliative radiotherapy was administered, and the disease remained stable for > 1 year. Our case illustrates a rare disease with an 8-year follow-up, involving different therapeutic strategies against multiple recurrences. J Drugs Dermatol. 2022;21(5):531-533. doi:10.36849/JDD.6583.