This study investigated the efficacy of single-phase dual-energy CT (DECT) in differentiating pulmonary hamartomas from malignant lung lesions using virtual non-contrast (VNC), iodine, and fat quantification. Forty-six patients with 47 pulmonary lesions (mean age: 65.2 ± 12.1 years; hamartomas-to-malignant lesions = 22:25; male: 67%) underwent portal venous DECT using histology, PET-CT and follow-up CTs as a reference. Quantitative parameters such as VNC, fat fraction, iodine density and CT mixed values were statistically analyzed. Significant differences were found in fat fractions (hamartomas: 48.9%; malignancies: 22.9%; p ≤ 0.0001) and VNC HU values (hamartomas: −20.5 HU; malignancies: 17.8 HU; p ≤ 0.0001), with hamartomas having higher fat content and lower VNC HU values than malignancies. CT mixed values also differed significantly (p ≤ 0.0001), but iodine density showed no significant differences. ROC analysis favored the fat fraction (AUC = 96.4%; sensitivity: 100%) over the VNC, CT mixed value and iodine density for differentiation. The study concludes that the DECT-based fat fraction is superior to the single-energy CT in differentiating between incidental pulmonary hamartomas and malignant lesions, while post-contrast iodine density is ineffective for differentiation.