Renal failure is one of the worst complications occurring in multiple myeloma (MM) patients. It does not affect survival if reverted by a prompt chemotherapy before the damage becomes irreversible; therefore, the early diagnosis of renal dysfunction is crucial. High and low molecular weight urinary proteins have proved to be helpful in diagnosing initial renal damage since they are more sensitive than urea and creatinine serum levels or creatinine clearance. We studied the renal function of 111 MM patients through serum creatinine, urea, urinary IgG, α1-microglobulin (α1-M), and albumin (Alb). Two successive controls were made in a subset of 30 patients, categorized in three groups (improved, stable, worsened) according to the behavior of tumor burden markers (bone marrow plasmacytosis, monoclonal component, and β2-microglobulin). In every group, we evaluated the behavior of urinary proteins. Renal dysfunction evaluated with serum parameters was present in 19 patients (17%), while if studied with urinary proteins was revealed in 71 patients (64.5%). Urinary proteins statistically correlated with each other. They correlated with creatinine, IgG, and α1-M also with urea. By contrast, they showed a variable correlation with clinical parameters: α1-M correlated with bone marrow plasmacytosis (BMPC) (p=0.02) and β2-M (p=0.000001), IgG with all three disease parameters (MC p=0.0005, BMPC p=0.009, β2-M p=0.007), and Alb only with β2-M (p=0.0004). In the subset of 30 patients followed with two successive controls, urinary proteins showed a parallel behavior with the indices of tumor burden. In conclusion, IgG, α1-microglobulin, and albumin are reliable and sensitive to precociously reveal renal damage, and we recommend their routine use for the definition and monitoring of renal function in multiple myeloma patients, mainly those in early stage, to better identify initial signs of progression.