The significance of loss of SOCS3, a negative regulator of signalling pathways including those of STAT3 and NF‐κB, was examined in mantle cell lymphoma (MCL). The protein expression and gene methylation status of SOCS3 were detected using immunohistochemistry/Western blots and methylation‐specific polymerase chain reaction, respectively. To evaluate its functional importance, SOCS3 was restored in two SOCS3‐negative MCL cell lines using a lentiviral vector. Loss of SOCS3 protein expression was found in 3/4 MCL cell lines and 18/33 (54·5%) tumours. SOCS3 was found consistently methylated in cell lines (3/4) and tumours (7/7) negative for SOCS3, and was unmethylated in all SOCS3‐positive cell line (1/1) and tumours (5/5) examined. Treatment of all three SOCS3‐negative cell lines with 2′‐deoxy‐5‐azacytidine restored SOCS3 expression. SOCS3 is biologically important in MCL, as lentiviral transfer of SOCS3 in SOCS3‐negative cell lines increased their apoptotic activity, downregulated nuclear factor (NF)‐κB‐p65, cyclin D1 (CCND1), BCL2 and BCL‐XL (BCL2L1), and substantially dampened interleukin 10‐induced STAT3 activation. In 19 patients aged ≤69 years at time of diagnosis, we found that those that carried SOCS3‐negative tumours showed a trend toward a worse outcome (P = 0·1, log‐rank).