[(99m)TC]sestamibi and [(99m)TC]tetrofosmin are two lipophilic cationic complexes which were originally employed in myocardial perfusion imaging and then later applied as tumor-seeking agents in the evaluation of diverse human malignancies. Despite the wider use of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) in cancer imaging, the two cationic lipophilic agents still play a useful clinical role in oncology when single-photon emission computed tomography (SPET) instead of planar is used as the acquisition method. This review summarizes the results of studies on the use of these radiopharmaceuticals in lung cancer, malignant lymphomas and brain tumors. Their performance in the diagnosis and staging of the primary tumor, the prediction of cancer response to therapy, the monitoring of treatment and the detection of recurrence during follow-up is also compared. Numerous studies have shown that SPET procedures are highly sensitive and accurate in tumor patient management. However, the main limitation to both SPET and planar imaging alike is that under some conditions the images do not give a clear structural delineation of the pathologic processes detected with these procedures. This sometimes makes SPET images difficult to interpret and so reduces its diagnostic performance. Recently available hybrid SPET/CT devices appear to overcome this problem by providing both functional and anatomical data. Preliminary reports on SPET/CT in tumor imaging have demonstrated that SPET/CT can provide more clinical information than SPET or CT alone in some cases. The possible role of integrated dual-modality images using SPET with SM or TF is also briefly discussed.