To investigate whether risk of relapse of endometrial hyperplasia persists many years after successful primary therapy and whether clinical or biological markers observed at primary diagnosis may predict relapse. A series of 57 women with endometrial hyperplasia received levonorgestrel-impregnated intrauterine system or oral progestin for three months during 1998-2000. Index biopsies were classified according to WHO1994 and D-score systems, and immunohistochemical staining for estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor A (PRA), progesterone receptor B (PRB), B-cell lymphoma 2/apoptosis regulator (BCL2), BCL2-associated X protein/apoptosis regulator (BAX), paired box 2 (PAX2), and phosphatase and tensin homolog (PTEN) reported as H-scores. Over a follow-up of 157.8 months, 23% (10/43) of patients experienced relapse. No correlation with age, body mass index, parity, WHO94 classification, or D-score was found. Only PRA (p=0.004) and PRB (p=0.038) showed certain correlation with relapse. Endometrial hyperplasia recurs many years after successful progestin therapy. Increased expression of PRB and reduced expression of PRA significantly correlated with relapse. Our results support the importance of continuous endometrial protection and the need for new clinical surveillance guidelines.