We present a case of squamous cell carcinoma (SCC) in the setting of Waldenström macroglobulinemia (WM). A 68-year-old male and daily marijuana smoker with recently diagnosed WM presented via telemedicine in 2020 for a progressively worsening sore throat and unintentional weight loss. Immunotherapy for WM was delayed due to the COVID-19 pandemic. In the clinic, examination revealed an indurated, tender midline mass at the base of the tongue, not limiting tongue mobility. The left level-II and right level-III lymph nodes were enlarged. The oropharyngeal lesion was biopsied, and pathology was consistent with human papillomavirus-positive (HPV+) SCC. Four cycles of concurrent chemotherapy and radiation for SCC were administered without delay, with an initial response. However, on surveillance, metastases to the brain and lungs were detected, and the patient was placed on palliative treatment as he did not meet eligibility for a clinical trial due to his WM. Concurrent WM and HPV+ SCC may have a worse prognosis, due to disease progression and reduced therapeutic options.