The growth pattern of pilocytic astrocytoma (PAs) is unpredictable. Gene expression profiling has recently demonstrated an inverse relationship between myelin basic protein (MBP) expression and progression free survival (PFS) in PAs. We present here the pattern of expression of oligodendroglial differentiation markers (ODMs) in PAs by immunohistochemistry and their correlation with PI and PFS. Sixty-four cases of PA were reviewed and representative sections were stained for Ki-67 and ODMs, including MBP, platelet-derived growth factor receptor-α (PDGFR-α), Olig-1, and Olig-2. Sections were graded semi-quantitatively for intensity (I: 0–3+) and extent (E: 0–4+) of staining. PI was expressed as a percentage of Ki-67 positive cells. Immunoreactivity of MBP, PDGFR-α, Olig-1, and Olig-2 was observed in 84, 56, 97, and 75% of cases, respectively. There was a statistically significant inverse correlation between MBP expression and PI (r ² = .696, p  = .014). A positive correlation was observed between PDGFR-α and PI (r ² = .727, p  = .011). Further analysis showed a significant difference in PFS between low expressors [I + E score ≤ 3] and high expressors (I + E score ≥ 4) for PDGFR-α with p  < .001. Notably, there was a significant difference in PFS between high expressors of MBP and high expressors of PDGFR-α with p  < .001. These results suggest that expression of ODMs, especially MBP and PDGFR-α, may identify two clinical subsets of PA. In addition, we have shown the expression of 4 different ODMs in PAs, which may support the possibility that PAs arise from oligodendrocyte progenitor/precursor cells probably similar to the O2A progenitor cells in the mouse.