Whole-body scintigraphy with Technetium-99m 2-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) has been proposed as a useful method for demonstrating the areas of active bone marrow infiltration in multiple myeloma (MM). In this study, we compared the (99m)Tc-MIBI scan with magnetic resonance imaging (MRI), skeletal X-ray survey, and biochemical markers of disease activity in MM to determine its potential in predicting the extension of the disease. Twenty-four myeloma patients had undergone to the (99m)Tc-MIBI scan. Only two patients showed negative results in the (99m)Tc-MIBI scan; one had clinically active disease, and the other was on remission. MRI was performed to 18 clinically active patients, and 16 of them showed positive myelomatous bone marrow involvement. No significant difference was found between the (99m)Tc-MIBI scan and MRI in predicting the extension of bone marrow infiltration in MM (p = 0.11). (99m)Tc-MIBI scores were correlated with bone marrow neoplastic plasma cell ratio (p = 0.005), serum paraprotein level (p < 0.001), serum lactate dehydrogenase (p = 0.031), and beta-2 microglobulin (p = 0.045). The (99m)Tc-MIBI scan showed disease activity better than the skeletal X-ray survey (x2 = 5.299, p = 0.021). A significant decrease was found in posttreatment (99m)Tc-MIBI scores of the patients with positive overall response (p = 0.016). The (99m)Tc-MIBI scan is a noninvasive test that can show the extension of the disease in MM. It seems that the (99m)Tc-MIBI scan and MRI show extension and intensity of the myelomatous bone marrow infiltration equally well. The (99m)Tc-MIBI scan can be an alternative to MRI when it is not available or if there is any limitations for its usage.