Neurodegeneration of the central and peripheral nervous system associated with hypocupremia and hyperzincinemia has been widely recognized but the origin of high zinc remained unknown. Denture cream has been recently suggested as one possible source of zinc, but the frequency with which denture fixative alone accounts for this syndrome is unknown. We analyzed the origin of excessive zinc in eleven patients with a progressive myelopolyneuropathy and unexplained hypocupremia with hyperzincinemia. These patients had a detailed clinical assessment, determination of zinc and copper levels, and analyzed use of denture cream with the estimates of daily zinc exposure. We identified denture cream as a source of excessive zinc in 100% patients in our cohort. They all had a history of ill-fitting dentures requiring large amounts of denture cream, resulting in significant zinc exposure. Their copper and zinc normalized after stopping denture cream, further confirming that this is the source of high zinc. Inappropriate use of denture cream appears to be the sole source of excessive zinc in these patients.