Background: Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis. Magnetic resonance imaging (MRI) remains the gold standard for non-invasive DIPG diagnosis. MRI features have been tested as surrogate biomarkers. We investigated the direct involvement of cranial nerve V (CN V) in DIPG at diagnosis and its utility as predictor of poor overall survival. Materials and Methods: We examined MRI scans of 35 consecutive patients with radiological diagnosis of DIPG. Direct involvement of CN V was assessed on the diagnostic scans. Differences in overall survival (OS) and time to progression (TTP) were analyzed for involvement of CN V, sex, age, tumor size, ring enhancement, and treatment regimen. Correlations between involvement of CN V and disease dissemination, magnet strength and slice thickness were analyzed. Statistical analyses included Kaplan-Meier curves, log-rank test and Spearman's Rho. Results: After excluding six long-term survivors, 29 patients were examined (15 M, 14 F). Four patients presented direct involvement of CN V. Histological data were available in 12 patients. Median OS was 11 months (range 3-23 months). Significant differences in OS were found for direct involvement of CN V (median OS: 7 months, 95% CI 1.1-12.9 months for involvement of CN V vs. 13 months, 95% CI 10.2-15.7 for lack of involvement of CN V, respectively, p < 0.049). Significant differences in TTP were found for the two treatment regimens (median TTP: 4 months, 95% CI 2.6-5.3 vs. 7 months, 95% CI 5.9-8.1, respectively, p < 0.027). No significant correlation was found between involvement of CN V and magnet strength or slice thickness (r = -0.201; p = NS). A trend toward positive correlation was found between direct involvement of CN V at diagnosis and dissemination of disease at follow-up (r = 0.347; p < 0.065). Conclusions: In our cohort, direct involvement of CN V correlated with poor prognosis. Based on our data, we suggest that in DIPG direct involvement of CN V should be routinely evaluated on diagnostic scans.