To investigate the effects of iterative reconstruction in 18F-fluorodeoxyglucose (FDG) gamma camera coincidence imaging (GCI), image contrast and visual detection obtained by using the iterative ordered-subsets expectation maximization (OSEM) reconstruction, in a phantom and in patients with lung cancer and breast cancer, were compared with those obtained by using the conventional filtered backprojection (FBP) reconstruction. Images of a cylindrical phantom containing hot spheres of various sizes (10-38 mm) were acquired by positron emission tomography (PET) and GCI at various sphere-to-background activity ratios. Forty-one consecutive patients with biopsy-proven cancer of lung (n = 20) and breast (n = 21) underwent PET and GCI on the same day after intravenous injection of 370 MBq of FDG. GCI images reconstructed by the OSEM and the FBP were compared. FDG PET was considered as the standard of reference. In GCI phantom images, OSEM yielded better contrast and signal-to-noise ratio (SNR) than FBP over the range of sphere sizes. Attenuation correction improved both the image measures and sphere detection obtained by the OSEM in GCI. In the study involving patients, FDG PET depicted 41 primary tumours and 25 metastatic lymph nodes. All of the tumours >2 cm in diameter (n = 25), six of the nine tumours 1.5-2.0 cm in diameter (67%), two of seven tumours <1.5 cm in diameter (29%), and 20 metastatic lymph nodes (80%) were detected in attenuation uncorrected GCI reconstructed by the OSEM as well as the FBP. The undetected lesions in GCI were identical between the OSEM and the FBP reconstructions. OSEM yielded significantly greater tumour-to-background (T/B) ratios and lower noise than FBP in GCI (T/B ratios, 4.1+/-3.2 vs 3.7+/-2.7, P = 0.02; noise, 0.09+/-0.04 vs 0.14+/-0.05, P<0.0001). In conclusion, OSEM yielded better image contrast and less noise than the FBP in GCI, but the lesion detection obtained by the OSEM and the FBP in attenuation uncorrected GCI in patients with lung cancer and breast cancer were similar. Phantom data suggest the potential of OSEM for improving lesion detection in GCI after attenuation correction.