Background Multiple myeloma (MM) is characterised by a presence of clonal plasma cell (a-PC) which are usually localised in bone marrow (BM) as a heterogeneous suspension, not often as solitary lesion. A BM microenvironment dependency is lost in a subset of patients and a-PCs spread out of BM, probably because of changes in adhesive molecules expression. Circulating myeloma PCs (cPCs) were detected in peripheral blood of almost all MM. Moreover, primary and/or secondary extramedullary disease (soft tissue and/or bone-related) was revealed in many patients. On the other hand, presence of a-PCs in cerebrospinal fluid (CSF) is relatively rare. Aim Detection of a-PCs in CSF and comparison of their phenotype with other compartments. Methods CSF of 15 relapsed MM patients was analysed by polychromatic flow cytometry (FC). Centrifuged samples were immediately incubated with MoAb (mostly CD38/CD138/CD45/CD19/CD56/CD14/CD5/CD27), lysed by NH4Cl and analysed. Results Whole group of analysed CSF has median of leukocytes 231 with range 19-6013. Myeloma a-PC infiltration was detected in 26.7 % (4/15). Only a-PCs were detected, these were always CD19- and in 50% CD56+. Phenotype profile in CSF, bone marrow, peripheral blood and tumour was similar according to CD19 and CD56. Flow cytometry is a highly efficient method for a-PCs detection. Conclusion Unfortunately, for these small samples more markers have to be analysed simultaneously to perform diagnostics and to analyse a-PCs as well, so only 8-colour FC is relatively insufficient in term of detail a-PC phenotype assess. All CSF+ patients were almost refractory to the treatment and they have cPCs in peripheral blood, extramedullary relapse was detected in 2 patients as well. It is evident, that prognosis of patients with CNS infiltration is generally poor. Supported by Ministry of Health of the Czech Republic, grant nr. 17-29343A. Multiple myeloma (MM) is characterised by a presence of clonal plasma cell (a-PC) which are usually localised in bone marrow (BM) as a heterogeneous suspension, not often as solitary lesion. A BM microenvironment dependency is lost in a subset of patients and a-PCs spread out of BM, probably because of changes in adhesive molecules expression. Circulating myeloma PCs (cPCs) were detected in peripheral blood of almost all MM. Moreover, primary and/or secondary extramedullary disease (soft tissue and/or bone-related) was revealed in many patients. On the other hand, presence of a-PCs in cerebrospinal fluid (CSF) is relatively rare. Detection of a-PCs in CSF and comparison of their phenotype with other compartments. CSF of 15 relapsed MM patients was analysed by polychromatic flow cytometry (FC). Centrifuged samples were immediately incubated with MoAb (mostly CD38/CD138/CD45/CD19/CD56/CD14/CD5/CD27), lysed by NH4Cl and analysed. Whole group of analysed CSF has median of leukocytes 231 with range 19-6013. Myeloma a-PC infiltration was detected in 26.7 % (4/15). Only a-PCs were detected, these were always CD19- and in 50% CD56+. Phenotype profile in CSF, bone marrow, peripheral blood and tumour was similar according to CD19 and CD56. Flow cytometry is a highly efficient method for a-PCs detection. Unfortunately, for these small samples more markers have to be analysed simultaneously to perform diagnostics and to analyse a-PCs as well, so only 8-colour FC is relatively insufficient in term of detail a-PC phenotype assess. All CSF+ patients were almost refractory to the treatment and they have cPCs in peripheral blood, extramedullary relapse was detected in 2 patients as well. It is evident, that prognosis of patients with CNS infiltration is generally poor. Supported by Ministry of Health of the Czech Republic, grant nr. 17-29343A.