The purpose of the present study was to identify a predictive marker associated with tumor progression or recurrence. We investigated the expression of p53, Ki-67, Bax, Bcl-2, vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) in pituitary adenomas (PAs) with/without tumor progression during follow-up periods. We compared the expression of these molecules in primary and recurrent specimens to identify a predictive marker associated with tumor progression. Nineteen patients had no progression for more than 5-years of follow-up. Nine patients had tumor progression within 5 years of their first transsphenoidal surgery (TSS) surgery and underwent re-TSS for treating progression of adenoma. Tumor size was larger and involvement of the cavernous sinus was more frequent in the progression group than these variables in the no progression group. A strong association was observed between NRP-1 expression and tumor progression. No significant risk for developing tumor progression was associated with Ki-67, p53, Bax, Bcl-2, VEGFR-1, VEGFR-2, or VEGF-A expression. Four of nine patients showed strong NRP-1 immunoreactivity in progression specimens. Negative NRP-1 immunoreactivity in the initial specimens was converted into strong positivity in the progression specimens of five patients. NRP-1 could be a relevant PA marker of progression and could be a potential target for medical therapy.