The experience of cancer represents a unique challenge to both the physical and psychological health of the individual. High levels of distress are common in cancer patients irrespective of the type of pathology. However, the physiological aspects of the disease process may be a source of confound in the psychiatric screening process, thereby reducing the accuracy of case identification. The current review examines the salient factors which should be considered by clinicians when screening for clinically significant psychological distress. The review will evaluate the strengths and limitations of contemporary screening instruments within this context and suggest approaches to maximize screening accuracy in this clinical group. Finally, the review will consider issues in the efficiency of the referral pathway to liaison psychiatry services for those patients positively screened. Implications for current psychiatric practice and the direction of future research are also discussed.