CD56, p53, and Cyclin D1 detection in plasma cells (PC) can help to predict prognosis of multiple myeloma (MM). Clinical and biochemical prognostic parameters were analysed in a group of 122 patients with primary diagnosed MM in the period 2011–2015. Bone marrow biopsies were analysed with Cyclin D1, p53, CD56 antibodies. Statistical analysis was performed using Microsoft Excel 2010 and Graph Pad Prism 5. Lack of CD56 expression and p53-positivity were significantly correlated with a low glomerular filtration rate (GFR), low platelet count and haemoglobin level, as well as with high serum creatinine levels. Patients with Cyclin D1 expression in PC had a significantly higher serum calcium level and more common osteolytic lesion in bones. CD56-negative as well as p53, Cyclin D1-positive groups had advanced Salmon–Durie MM stages by and significantly higher ß2-microglobulin. Expression of p53, Cyclin D1 and lack of CD56 antigen in PC are negative predictive factors in cases of MM, as these patients were diagnosed as having late Salmon–Durie stage and higher ß2-microglobulin level. Expression of p53 and lack of CD56 antigen in PC is associated with an increased creatinine level in blood and decreased GFR; therefore, these are criteria for chronic renal failure progression and poorer prognosis of MM.