Patients with squamous cell cancer (SCC) of the head and neck are at increased risk for second primary malignancies (SPMs). We report on a 53-year-old patient with primary diagnosis of SCC in the anterior floor of the mouth. Panendoscopy suspected an SPM of the right vocal cord. FDG PET/CT, as a whole-body imaging method, confirmed this suspicion and raised concern for further SPM of both esophagus and colon. All malignancies were confirmed by biopsy. Subsequently, the patient underwent radiochemotherapy. In summary, FDG PET/CT revealed unexpected multiple SPMs, prevented unnecessary resection of the oral SCC, and enabled individualized therapeutic management.