Gardner syndrome is a rare genetic disorder within the familial adenomatous polyposis spectrum, characterized by intestinal polyposis, osteomas, and cutaneous tumours. Epidermoid cysts, its most frequent skin manifestation, often emerge early in life, serving as vital diagnostic clues.

We present a case of a 38-year-old male with a 30-year history of progressively enlarging skin swellings, lower back pain, dental issues, and blood-stained stool. The diagnostic workup was comprehensive. Clinical evaluation and histopathology were primarily used to assess the cutaneous lesions. To investigate gastrointestinal symptoms, a colonoscopy with multiple targeted tissue biopsies was performed. Extensive radiological imaging mapped skeletal anomalies, utilizing panoramic X-rays for the jaw, 3D CT reconstructions of the skull, an abdominal-pelvic CT scan, and radiographs of the long bones. Baseline laboratory tests, an abdominal ultrasound, and ophthalmoscopy were additionally conducted to rule out other extracolonic manifestations.

Histopathological analysis confirmed the skin lesions as giant epidermoid cysts, including a debilitating 15 × 10 cm cyst on the lower back. Colonoscopy identified over 30 benign adenomatous polyps spanning the colon. Imaging revealed multiple cranial osteomas, mandibular sclerosis, and hypodontia. Blood tests, thyroid ultrasound, and retinal exams returned normal results. Interventions included staged surgical excisions of the cysts, psychosocial counselling, and a referral to general surgery for a prophylactic laparoscopic pan-colectomy.

In conclusion, multiple epidermoid cysts are crucial early indicators of Gardner syndrome. Prompt recognition enables vital gastroenterological interventions—such as prophylactic colectomy—to prevent colonic malignancy, while surgical management of the cysts directly addresses the patient’s physical and psychosocial burdens.