Improved accuracy in oncological computed tomography (CT) could lead to a decrease in morbidity and improved survival for oncology patients. Visualization of metabolic activity using the glucose analogue [(18)F]fluorodeoxyglucose (FDG) in combination with the high anatomic resolution of CT in an integrated positron emission tomography (PET)/CT examination has the highest sensitivity and specificity for the detection of primary and metastatic lesions. However, PET/CT costs are high and patient access is limited; thus CT remains the primary imaging modality in oncology patients. We have noted that subtle lesions are more easily detected on CT by radiologists with PET/CT experience. We aimed to provide a brief review of the literature with comparisons of multi-detector computed tomography (MDCT) and PET/CT in primary and metastatic disease with an emphasis on findings that may be overlooked on MDCT in cancer of the breast, lung, colon, and ovaries, and in melanoma, as well as thrombosis in oncology patients. We further reviewed our experience for illustrative comparisons of PET/CT and MDCT studies. Experience in interpreting conventional CT scans alongside PET/CT can help the reader develop an appreciation for the subtle appearance of some lesions on CT that might otherwise be missed. This could improve detection rates, reduce errors, and improve patient management.