Objective. We present a successful multidisciplinary treatment approach used for a patient with rapidly developing, high-volume, and high-risk squamous cell carcinomas (SCCs), addressing short-term treatment, long-term maintenance, and appropriate preventative strategies in a difficult patient population. Case report. An immunocompetent, 84-year-old, Caucasian man with at least 30 SCCs of the scalp, head, neck, and upper extremities, including a 4-cm SCC on the vertex of the scalp infiltrating to the periosteum, presented to a cutaneous oncology clinic. Initial physical examination revealed nearly confluent, erythematous, hyperkeratotic, crusted papules and plaques on the head, neck, back, arms, and dorsal hands, all of which were clinically obvious SCC. Nonlesional skin displayed widespread epidermal dysplasia. The patient was seen by the clinic's medical oncology and dermatology teams in coordinated dual visits. The invasive scalp lesion was treated by Mohs surgery and radiation, and the large SCC and field cancerization were successfully treated with a combination of topical and intralesional 5-fluorouracil with pulsed oral capecitabine, which resulted in a significant reduction in SCC disease burden. Conclusion. Management of patients with overwhelming numbers of SCCs is extremely challenging. Combination topical and/or intralesional 5-fluorouracil and oral capecitabine may be considered as part of the management approach when mechanical destruction and surgery alone are not feasible. Multidisciplinary care coordinated between the surgeon, dermatologic oncologist, medical oncologist, and radiation oncologist is essential for providing comprehensive treatment and deploying preventative strategies in this population at high risk for metastatic SCC formation.