Objectives Mantle cell lymphoma (MCL) is one of the most heterogeneous lymphoid neoplasms with a variable course of disease. Although t(11;14)(q13;q32) is the hallmark of MCL resulting in cyclin D1 (CCND1) overexpression in 90% of patients, this is difficult to validate by immunohistochemistry. We hypothesised that SOX11 could be a robust molecular biomarker for MCL. Methods We have developed very sensitive and specific RT‐qPCR assay employing a poly‐A specific RT primer to circumvent contamination from gDNA caused by the intron‐less nature of SOX11. Results We found a significant difference between the expression levels of SOX11 in patients with MCL at diagnosis (n = 21) and in healthy donors (n = 18) (blood: P < 0.0001; marrow: P = 0.0001). SOX11 expression of very low levels close to the assay sensitivity was detected in only 2 of 18 healthy donors, while low levels of CCND1 expression was observed in all blood and 12 of 13 marrow samples within the defined detection limit of Cq = 40. In spiking experiments of the GRANTA‐519 MCL cell line into mononuclear cells from normal donor, the sensitivity of the SOX11 assay was found to be 2 × 10−4, while the sensitivity of the CCND1 assay was estimated to 2 × 10−3 because of the normal background expression. In longitudinal sampling from patients with MCL the minimal residual disease (MRD) values based on the SOX11 expression mirrored the clinical disease development. Conclusion This SOX11 RT‐qPCR assay could be a useful tool for MRD monitoring in patients with MCL.