The combined presence of two cancers in a single patient is rare. Usually, the second cancer is caused by immunosuppression resulting from treatment (chemotherapy, radiotherapy) of the first neoplasia. Multiple myeloma and kidney cancer share similar risk factors (obesity, smoking, hypertension), and several cases involving the combination of these two neoplasias have been described in the literature. We are reporting, for the first time, two clinical cases involving the combined presence of multiple myeloma and clear cell renal cell carcinoma discovered synchronously, with concomitant bone recurrence some time after the initial diagnosis. Pathophysiological mechanisms have been described that are common to renal carcinoma and multiple myeloma; in particular, the role of interleukin-6, which is produced by the renal cells and stimulates the proliferation of myeloma cells. Clinicians must be aware of the possibility of this disease combination and, in the event of an obvious recurrence of one of these two diseases, should search systematically for recurrence of the other disease.