Abstract Background Pseudoprogression refers to areas of enhancement on MRI postadjuvant chemoradiation that arise as a result of treatment-related effects. Pseudoprogression has been well described with temozolomide-based chemoradiation but has not been studied in the setting of procarbazine, lomustine, and vincristine (PCV) chemotherapy. We reviewed patients treated with PCV to investigate the occurrence of pseudoprogression. Methods Adults diagnosed with World Health Organization grade II or III gliomas between 2010 and 2015 and treated with PCV or temozolomide were identified. Patient, tumor, treatment, and MRI data were retrospectively collected and analyzed. Pseudoprogression was defined as new enhancement seen on MRI within 6 months of completion of adjuvant radiotherapy or concurrent chemoradiation, which improved or remained stable on subsequent scans without therapeutic intervention. If MRI showed areas of new enhancement outside the 6-month post-treatment window, which resolved or remained stable without treatment, or in patients who did not receive adjuvant treatment, it was referred to as “atypical pseudoprogression.” Results Fifty-seven patients were identified. Nine (16%) patients were identified as having pseudoprogression on MRI. Two (4%) of these patients were treated with PCV and 7 (12%) were treated with temozolomide. Seventeen (30%) patients had atypical pseudoprogression: 8 (14%) treated with temozolomide, 8 (14%) treated with PCV, and 1 (2%) treated with both types of chemotherapy. Conclusions We describe the first 2 cases of PCV-related pseudoprogression and 17 cases of atypical pseudoprogression. As the re-emergence of adjuvant PCV occurs in clinical practice, the occurrence of classical and atypical pseudoprogression could have a significant impact on clinical decision making.