The aim of this pilot study was to determine the plasma levels of monocyte chemotactic protein-1 (MCP-1) and possible associations with angiogenesis and the main clinical features of untreated patients with multiple myeloma (MM). ELISA was used to determine plasma MCP-1 levels in 45 newly diagnosed MM patients and 24 healthy controls. The blood vessels were highlighted by immunohistochemical staining, and computer-assisted image analysis was used for more objective and accurate determination of two parameters of angiogenesis: microvessel density (MVD) and total vascular area (TVA). The plasma levels of MCP-1 were compared to these parameters and the presence of anemia, renal dysfunction, and bone lesions. A significant positive correlation was found between plasma MCP-1 concentrations and TVA (p = 0.02). The MCP-1 levels were significantly higher in MM patients with evident bone lesions (p = 0.01), renal dysfunction (p = 0.02), or anemia (p = 0.04). Therefore, our preliminary results found a positive association between plasma MCP-1 levels, angiogenesis (expressed as TVA), and clinical features in patients with MM. However, additional prospective studies with a respectable number of patients should be performed to authenticate these results and establish MCP-1 as a possible target of active treatment.