Objective: To evaluate, immunohistochemically expression of cyclin D1 in myeloma cells in the bone marrow of multiple myeloma (MM) patients treated with bortezomib and compare obtained data with clinico-pathological parameters and response to therapy. Patients and methods: Twenty four patients with MM treated with bortezomib were included in this study. To determine the expression of cyclin D1 in the bone marrow prior to and after bortezomib treatment, we used double immunohistochemical method, which allows simultaneous staining of the sample with two antibodies (in this case with CD138 (plasma cell marker) and cyclin D1). A positive reaction was considered when ≥ 10% plasma cells showed cyclin D1 nuclear staining, at any intensity. The results were correlated with patient’s clinicopathological data. Results: The nuclear expression of cyclin D1 in the plasma cells of patients with MM before therapy was found in 9/24 cases and there was 15/24 negative patients, including patients without any nuclear staining 13/24 or with nuclear staining for cyclin D1 but in < 10% of plasma cells 2/24. After bortezomib tretament, 5/24 patients were positive for cyclin D1 while 19/24 patients were negative, including patients without any nuclear staining 17/24 or they had < 10% of cyclin D1 positive tumor cells 2/24. In this study there was no statistically significant difference in the expression of cyclin D1 before and after bortezomib treatment (p = 0.084) as well as any correlation with some of the clinical or pathological parameters. Conclusion: The results and the level of expression of cyclin D1 vary within different study groups and depend as well on the prior treatment patients received. Therefore to determine the prognostics significance of cyclin D1 expression and its correlation with clinico-pathological features a larger and more homogeneous group of patients is required.