The rapid development of fluorescence in situ hybridization (FISH) karyotyping led to the discovery of the significant prognostic impact of certain chromosomal abnormalities on the course of Multiple Myeloma (MM). Additionally, high blood lactate dehydrogenase (LDH) levels have been connected to shorter survival periods, more aggressive malignancies, enhanced cell proliferation, and extramedullary illnesses. This study aims to evaluate the prognostic significance of the R-ISS according to plasmacytoma presentation in newly diagnosed MM patients. Retrospective methods were used to conduct this investigation. A total of 166 consecutive patients with newly diagnosed MM and treated in our tertiary care center between the years 2009 and 2023 were evaluated. Of the 166 individuals who were included in this research, 35 (21.1%) had plasmacytomas at diagnosis. Plasmacytoma was not detected in 131 (78.9%) patients at diagnosis. The mean age was 56.8 ± 7.5 for all patients. The age of the patients without plasmacytoma at diagnosis was statistically significantly higher than patients with plasmacytoma at diagnosis (p: 0.04). No statistically significant difference was observed in terms of OS and DFS in the R-ISS 1, 2, and 3 groups in patients with and without plasmacytoma at diagnosis. Due to this study’s results, we think that more needs to be done regarding the R-ISS classification. Perhaps it would be more effective to include other factors in risk classification, such as age, gender, and the presence of plasmacytoma and lytic lesions.