Recently, low-dose 5-fluorouracil/cisplatin induction concurrent with radiation (chemoradiation) has been reported to be effective for locally advanced squamous cell carcinoma of the otorhinolaryngologic and gynecologic regions. However, to date, this therapeutic option has not been evaluated for squamous cell carcinoma of the skin. We evaluated chemoradiation therapy using cisplatin and 5-fluorouracil in two patients with locally advanced squamous cell carcinoma of the skin. Administration of cisplatin and 5-fluorouracil was conducted concurrently with conventionally fractionated radiation therapy. Cisplatin (patient 1: 4 mg/m²/d on days 1 to 5; patient 2: 15 mg/m²/d on days 1 to 5) and 5-fluorouracil (patient 1: 400 mg/m²/d for 7 days; patient 2: 850 mg/m²/d for 5 days) were administered intravenously for 1 hour and for 24 hours, respectively. Patient 1 underwent two courses of chemotherapy with a 3-week interval, and patient 2 underwent a single course of chemotherapy. The primary tumor of both patients showed complete regression, leaving ulceration. In patient 1, the ulceration completely resolved after 3 months. Patient 2 underwent surgical resection and full-thickness skin grafting. A histopathologic examination confirmed complete tumor regression. Neither patient suffered any serious side effects during this treatment. We conclude that chemoradiation using cisplatin and 5-fluorouracil was effective in these two patients with locally advanced squamous cell carcinoma of the skin. Several randomized studies have shown concurrent chemoradiation to be superior to radiation alone. This regimen is an option in managing patients who have unresectable primary tumors or who require preservation of local function.