A 52-year-old male developed multiple skin ulcers/purpura in the bilateral lower limbs. A detailed examination led to a diagnosis of type I cryoglobulinemia-related skin lesions, with smoldering multiple myeloma (SMM) as a background disease. After 5 years, dermal symptoms became severe. Although there were no multiple myeloma (MM)-related symptoms other than the skin, induction therapy with bortezomib and dexamethasone (BD) was performed. Since dermal symptoms and SMM responded well to treatment, high-dose chemotherapy (melphalan) with autologous peripheral blood stem cell transplantation (ASCT) was subsequently performed. There were no serious treatment-associated adverse events. In addition, a marked response was achieved, and the disease state was stable for ≥24 months. Only a few similar case reports have been reported to date. According to a recent study, when type I cryoglobulinemia becomes symptomatic, the treatment of respective hematological diseases as a background factor and patient-matched individualized treatment should be performed. The present case suggests that it is a feasible, safe and effective treatment strategy to consider the eligibility for high-dose chemotherapy with ASCT and then perform it, even for SMM-associated type I cryoglobulinemia.