The neurobiological basis of suicidal behaviour is multifactorial and complex. Several lines of evidence indicate that environmental factors as well as multiple genes and interactions of both are implicated in its aetiology. The aim of this study was to establish the transcriptomic expression profile of post-mortem brain tissue of suicide victims in order to identify new candidate genes and biological patterns for suicidal behaviour. Post-mortem orbitofrontal cortex tissue was derived from 11 suicide victims and 10 non-psychiatric controls carefully selected from a brain bank of over 150 brains, and the expression of more than 23000 messenger RNAs was assessed in this case-control study. Validation experiments were carried out using quantitative RT–PCR as an independent method. A classification of the differentially expressed genes according to their biological function and statistical analyses of the data were performed in order to identify biological pathways that are over-represented in the suicide group. In total, 124 transcripts demonstrated significant changes (fold changes ⩾1.3, p value ⩽0.01), with 59 showing under-, and 65 over-expression in the suicide group. The results could be validated for nine particularly interesting transcripts (CDCA7L, CDH12, EFEMP1, MLC1, PCDHB5, PTPRR, S100A13, SCN2B, and ZFP36). The pathway analysis showed that the Gene Ontology categories ‘central nervous system development’, ‘homophilic cell adhesion’, ‘regulation of cell proliferation’ and ‘transmission of nerve impulse’ were significantly enriched. The differentially expressed genes and significant biological processes might be involved in the pathophysiology of suicide and warrant further attention.