Cutaneous squamous cell carcinoma has presented an increasing burden globally, with the
occurrence of metastatic cutaneous squamous cell carcinoma being a relatively rare event but
presenting with significant challenges in management, and a paucity of treatment options.
Waldenström’s macroglobulinemia is similarly an infrequent diagnosis. We present a rare case
of a synchronous diagnosis of cutaneous squamous cell carcinoma and Waldenström’s macroglobulinemia with an associated lung mass with squamous differentiation. The considered
origin of the lung mass was either metastatic cutaneous squamous cell carcinoma or a primary squamous cell carcinoma of the lung, representing a third primary malignancy. The report highlights complexities in diagnosis and management, particularly in a patient with multiple synchronous malignancies. It further emphasizes the need for expanded global
availability of specific therapies, including PD-1 inhibitors.