To compare the epidemiological, clinical, and pathological features of follicular (FVPTC) and classical (CVPTC) variants of papillary thyroid cancer and to correlate their outcomes according to different features. Retrospective analysis of FVPTC and CVPTC patients selected at the moment of surgical treatment from 1999 to 2004, with a median follow-up of 15 years. Several significant differences were found between FVPTC and CVPTC such as the mean age at diagnosis, the presence of tumor capsule, the presence of thyroid capsule invasion, the presence of perithyroid soft tissue invasion, the lymph node metastases, the multifocality and bilaterality. At the end of follow-up only 9% (77/879) patients were not cured. However, a statistically significant lower percentage of persistent disease was found in the FVPTC than in the CVPTC group (3% vs. 14.5%, respectively, p < 0.0001). In multivariate analysis, the absence of the tumor capsule (OR = 6.75) or its invasion (OR = 7.89), the tumor size ≥4 cm (OR = 4.29), the variant CVPTC (OR = 3.35), and the presence of lymph node metastases (OR = 3.16) were all independent risk factors for the persistence of the disease. Despite an overall excellent prognosis of both variants, a higher percentage of CVPTC than FVPTC patients had a persistent disease. The absence of tumor capsule or its invasion, the tumor size ≥4 cm and the presence of lymph node metastases are other prognostic factors for the persistence of the disease. In contrast, the presence of an intact tumor capsule is the only good prognostic factor for their outcome.