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This case describes a woman in her mid-40s with recurrent colorectal cancer who developed severe dermatologic toxicity during panitumumab-based therapy. Three months after treatment initiation, she developed a diffuse acneiform eruption, pronounced xerosis and painful periungual inflammation with exuberant granulation tissue consistent with epidermal growth factor receptor (EGFR)-inhibitor–induced paronychia. Multidisciplinary, guideline-concordant supportive care (including prompt topical measures and short-course systemic therapy) achieved symptom control and allowed continuation of anticancer treatment. This report underscores the importance of early recognition and structured management of EGFR-inhibitor toxicities to prevent treatment disruption and preserve quality of life.