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Tumor proliferation has prognostic value in resected early-stage non-small cell lung cancer (NSCLC). We evaluated whether [F-18]fluorodeoxyglucose (FDG) uptake of NSCLC correlates with tumor proliferation and, thus, could noninvasively grade NSCLCs (refining patient prognosis and therapy). Thirty-nine patients with potentially resectable NSCLC underwent whole-body FDG positron emission tomography (PET) 45 min after i.v. injection of 10 mCi of FDG. Tumor FDG uptake was quantitated with the maximum pixel standardized uptake value (maxSUV). The lesion diameter from computed tomography was used to correct the maxSUV for partial volume effects using recovery coefficients determined for the General Electric Advance PET scanner. Thirty-eight patients underwent complete surgical staging (bronchoscopy and mediastinoscopy, with or without thoracotomy). One stage IV patient by PET underwent bronchoscopic biopsy only. Immunohistochemistry for Ki-67 (proliferation index marker) was performed on all of the 39 NSCLC specimens (35 resections, 1 percutaneous, and 3 surgical biopsies). The specimens were reviewed for cellular differentiation (poor, moderate, well) and tumor type. Lesions ranged from 0.7 to 6.1 cm. The correlation found between uncorrected maxSUV and lesion size (Rho, 0.56; P = 0.0006) disappeared when applying the recovery coefficients (Rho, -0.035; P = 0.83). Ki-67 expression (percentage of positive cells) correlated strongly with FDG uptake (corrected maxSUV: Rho, 0.73; P < 0.0001). The correlation was stronger for stage I lesions (11 stage IA, 15 stage IB): Rho, 0.79; P < 0.0001) and strongest in stage IB (Rho, 0.83; P = 0.0019). A significant association (P < 0.0001) between tumor differentiation and corrected SUV was noted. FDG PET may be used to noninvasively assess NSCLC proliferation in vivo, identifying rapidly growing NSCLCs with poor prognosis that could benefit from preoperative chemotherapy.