The search for biomarkers to detect the earliest glimpse of cancer has been one of the primary objectives of cancer research initiatives. These endeavours, in spite of constant clinical challenges, are now more focused as early cancer detection provides increased opportunities for different interventions and therapies, with higher potential for improving patient survival and quality of life. With the progress of the omics technologies, proteomics and metabolomics are currently being used for identification of biomarkers. In this line, cytoglobin (Cygb), a ubiquitously found protein, has been actively reviewed for its functional role. Cytoglobin is dynamically responsive to a number of insults, namely, fibrosis, oxidative stress, and hypoxia. Recently, it has been reported that Cygb is downregulated in a number of malignancies and that an induced overexpression reduces the proliferative characteristics of cancer cells. Thus, the upregulation of cytoglobin can be indicative of a tumour suppressor ability. Nevertheless, without a comprehensive outlook of the molecular and functional role of the globin, it will be most unlikely to consider cytoglobin as a biomarker for early detection of cancer or as a therapeutic option. This review provides an overview of the proposed role of cytoglobin and explores its potential functional role as a biomarker for cancer and other diseases.