The aim of this study was to evaluate the in vivo performance of a prototype dual-crystal [lutetium oxyorthosilicate (LSO)/sodium iodide (NaI)] dual-head coincidence camera (DHC) for PET and SPET (LSO-PS), in comparison to BGO-PET with fluorine-18 fluorodeoxyglucose (FDG) in oncology. This follows earlier reports that LSO-PS has noise-equivalent counting (NEC) rates comparable to partial ring BGO-PET, i.e. clearly higher than standard NaI DHCs. Twenty-four randomly selected oncological patients referred for whole-body FDG-PET underwent BGO-PET followed by LSO-PS. Four nuclear medicine physicians were randomised to read a single scan modality, in terms of lesion intensity, location and likelihood of malignancy. BGO-PET was considered the gold standard. Forty-eight lesions were classified as positive with BGO-PET, of which LSO-PS identified 73% (95% CI 60-86%). There was good observer agreement for both modalities in terms of intensity, location and interpretation. Lesions were missed by LSO-PS in 13 patients in the chest ( n=6), neck ( n=3) and abdomen ( n=4). The diameter of these lesions was estimated to be 0.5-1 cm. Initial results justify further evaluation of LSO-PS in specific clinical situations, especially if a role as an instrument of triage for PET is foreseen.