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With the continuing increase in the incidence of skin cancer, delivery of cost-efficient skin cancer treatment is a top priority.To compare costs associated with removal of skin cancers using Mohs micrographic surgery (MMS) with that using standard surgical excision (SSE) with frozen or permanent margin control in the office or an ambulatory surgery center (ASC).Costs for actual MMS and calculated costs for all SSE were recorded. The expense of treatment of incomplete excisions with subsequent reexcision and reconstruction and MMS on recurrent tumors were added to the final estimate.Four hundred six tumors were included in the study. An average tumor was cleared in 1.6 stages. MMS was the least expensive surgical procedure evaluated, at $805 per tumor. SSE with permanent margins ($1,026) was more expensive than MMS but less expensive than SSE with frozen margins ($1,200) and ASC-SSE with frozen margins ($2,507). Adjusted for inflation, the cost of MMS, inclusive of initial examination, biopsy, and 5-year follow-up, in 2009 ($1,376) was lower than in 1998 ($1,635).This study confirms MMS as the cornerstone of cost-effective treatment, regardless of place of service or type of margin control pathology.