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Background. For preservation of integrity of appearance and function in a 57-year-old male with a squamous cell carcinoma of his left big toe who had refused amputation, intra-arterial infusion with methotrexate was used. Objective. To evaluate the effectiveness of arterial infusion with methotrexate in this uncommon big toe cancer. Methods. Left external iliac arterial catheterization and infusion with methotrexate (50 mg) were used every 24 hours plus simultaneous intramuscular injection of 6 mg of leucovorin every 6 hours for 8 days. Results. At 7 years and 3 months after therapy, the patient was in sustained complete remission with a functionally normal left foot. Conclusion. This case study suggests that intra-arterial infusion chemotherapy is a simple and effective method for big toe squamous cell carcinoma with the unique advantage of preservation of organ and function. It can be considered as an effective alternative treatment. [ABSTRACT FROM AUTHOR]