Temozolomide is a chemotherapeutic drug that is mainly used in the treatment of primary glioblastoma multiforme and recurrent high‐grade glioma. Here, we report an efficient good manufacturing practice compliant method for the synthesis of [3‐N‐11C‐methyl]temozolomide from 3‐N‐hydroxymethyl temozolomide that cleaves off formaldehyde in situ and becomes activated towards alkylation with [11C]methyl iodide. The labelling method was developed for an on‐going patient study in which the predictive value of [3‐N‐11C‐methyl]temozolomide and positron emission tomography on the outcome of temozolomide treatment is being investigated. The precursor was reacted with [11C]methyl iodide in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene in acetonitrile, heated at stepwise increasing temperature. Purification by semipreparative HPLC with pharmaceutical grade eluent and filtration gave approximately 10 mL sterile product solution ready for injection containing 1.55 ± 0.38 GBq (n = 5), the specific activity was 88 ± 25 GBq/µmol and the radiochemical purity was 98.5 ± 1.9%. 13C‐NMR spectroscopy confirmed the labelled position after colabelling with 11C and 13C.