Purpose Mantle cell lymphoma (MCL) is a rare non-Hodgkin’s lymphoma entity with a poor prognosis. Therapeutic advances have improved the survival of patients enrolled in clinical trials; however, their impact on patients outside clinical trials remains unclear. In this work, we compared patient outcome inside and outside clinical trials. Methods We identified MCL patients recorded in six French population-based registries between 2008 and 2012 to perform a comparison with patients enrolled in two prospective multicenter MCL clinical trials conducted by the LYSA group during the same period. Variables associated with inclusion in a clinical trial were identified using a logistic regression. Pohar-Perme estimator and Nelson et al. flexible parametric model was used to estimate net survival probabilities and prognosis factors on excess mortality. Results A total of 312 registry patients were compared to the 372 patients enrolled in LYSA clinical trials. Patients included in clinical trials were younger (median age 60 vs 74, p < 0.001). Age and Ann Arbor stage IV were independently associated with enrollment [OR = 0.09 (0.06–0.12) and OR = 1.61 (1.11–2.34), respectively]. The 4 year net survival was better in clinical trials [79.9% (75.9–84.7) vs 60.3% (53.6–67.0)]. This result was confirmed in multivariate analysis in patients older than 65 years with a lower excess mortality rate [0.33 (0.17–0.66)]. Conclusions MCL included in trials are highly selected patients who are not representative of MCL patients who are encountered in everyday practice. With widened inclusion criteria, clinical trial patients could be more representative of the general population.