The invention relates to the diagnosis and management of cancer-related fatigue (CRF). More specifically the invention relates to identification and measurement of a single Biomarker or a group of biomarkers (e.g. genes) that are associated with cancer related fatigue. The identification and measurement of such biomarkers can be utilized in the diagnosis and management of fatigue and may facilitate the development of therapy for such fatigue. In particular, the invention provides for a method of diagnosing a subject with CRF by detecting expression of at least one gene associated with CRF in a sample obtained from the subject; and comparing expression of the gene to a control. The invention also describes a method of treating a patient with CRF by administering to the subject an agent that alters expression or activity of a gene associated with CRF. Further provided in the invention is array that includes a plurality of genes associated with CRF, such as TNFRSF25, SLC6A8, OGT, SNCA, APBA2, CASK, OR2W3, MYL4, IL7R, ARHGEF10 and ITGA6. Some of these genes are over expressed in a CRF patient (e.g., SNCA and SLC6A8) while others (e.g., IL7R, ARHGEF10) are under expressed. The array can provide detailed and comprehensive information that can result in improved diagnostics and in increased options for therapeutic treatment.