Craniopharyngioma often recurs after resection resulting in poor outcome for the affected patients. The reliable criteria for predicting the tumor behavior are still lacking. It has been suggested that proliferative potential of the tumor cells is necessary for recurrence. Present study evaluated the cell multiplication activity, which is possibly related to relapse in 32 patients with adamantine epithelioma (AE) and 31 patients with squamous papillary tumor (SP). For this tissue specimens from their primary and recurring tumors were collected and immunohistochemical analysis of the expression of minichromosome maintenance protein 6 (MCM6) and DNA topoisomerase II alphalpha (DNA Topo II alpha) in the tumor sections was performed by quantitative microscopy. It was found that the MCM6 label index (LI) was significantly higher in AE than that of SP, and in the primary tumors of both subtypes the LIs of tumors with recurrence were higher than those without recurrence. There was a strong linear positive correlation between MCM6 LI and DNA Topo II alpha LI (r = 0.713; p = 0.000) in the craniopharyngiomas studied. The median MCM6 LI of the total 20 recurrent craniopharyngiomas (31.49%) was not significantly different from that of their primary tumors (29.65%). The long term risk of tumor recurrence is higher in AE than SP and it is associated with MCM6 and DNA Topo II alpha expression.