The Anterior Cingulate Cortex (ACC, Brodmans Area 24) is implicated in the pathogenesis of schizophrenia due to its normal functions and connectivity together with reports of structural, morphological and neurotransmitter aberrations within this brain area in the disease state. Two-dimensional gel electrophoresis (2DE) was employed to scan and compare the ACC gray matter proteomes between schizophrenia (n = 10) and control (n = 10) post-mortem human tissue. This proteomic approach has detected 42 protein spots with altered levels in the schizophrenia cohort, which to our knowledge is the first proteomic analysis of the ACC in schizophrenia. Thirty nine of these proteins were subsequently identified using mass spectrometry and functionally classified into metabolism and oxidative stress, cytoskeletal, synaptic, signalling, trafficking and glial-specific groups. Some of the identified proteins have previously been implicated in the disease pathogenesis and some offer new insights into schizophrenia. Investigating these proteins, the genes encoding these proteins, their functions and interactions may shed light on the molecular mechanisms underlying the heterogeneous symptoms characteristic of schizophrenia.