Plasmacytoma is characterized by a local accumulation of monoclonal plasma cells without criteria for multiple myeloma ( MM ). The current treatment regimen is local radiotherapy. However, more than 50% of patients develop MM within 2 years after treatment. A population‐based registry was consulted for the diagnosis of solitary plasmacytoma between 1988 and 2011. Progression to MM and prognostic features for progression to MM were scored, including hypoxia inducible factors ( HIF ), vascular endothelial growth factor ( VEGF , also termed VEGFA ) and micro‐vessel density ( MVD ) expression in biopsy material. A total of 76 patients were included, 34% having extramedullary plasmacytoma ( EMP ) while 66% had a solitary plasmacytoma of the bone ( SBP ). Median follow‐up was 89 months, (7–293 months). In Seventy per cent of SBP patients developed MM with a median time to progression of 19 months (5–293). Three patients (12%) with EMP developed MM . High expression of VEGF and HIF ‐2α (also termed EPAS 1) was demonstrated in conjunction with an increased MVD in 66% of the patients. No association could be shown between angiogenesis parameters and progression to MM . In conclusion, this population‐based study demonstrates that SBP patients have a higher risk of developing MM following local radiotherapy, indicating that this group might benefit from added systemic chemotherapy.