Background: Cigarettes, food, water, and air pollution can contain toxic heavy metals, such as cadmium (Cd), arsenic (As), mercury (Hg), and lead (Pb). A cigarette contains approximately 1-2 ug of Cd, 40-120 ng of As, 2.95-10.2 ng of Hg, and 1-2 mg/kg of Pb because the tobacco plant concentrates metals from soil and water. The accumulation of toxic heavy metals inhaled from smoking may be associated with lung cancer. We surveyed tissue from current/former smokers with non-small cell lung cancer (NSCLC) for heavy metal content. Methods: Tissue collected from treatment-naïve stage I and II NSCLC patient samples that underwent surgical resection was analyzed by inductively coupled plasma mass spectroscopy (ICP-MS) for concentration of Cd, As, Hg, and Pb. 16 cases were matched for stage, histology, gender, age, and race. Concentrations were measured from two 20 micron thick slides each from formalin-fixed, paraffin-embedded (FFPE) tissues: primary lung cancer, benign adjacent lung, and where applicable to malignant lymph node, benign adjacent lymph node, benign lymph node, and distant non-malignant lung tissue. Negative controls were paraffin without tissue from FFPE blocks. Paired samples t-tests were used to make intra-case comparisons. The nonparametric Mann-Whitney U and the Wilcoxon signed-rank test were used to examine inter-case differences. Results: The median patient age was 64.7 (range 36.4-75.4). There were 15 primary lung cancer cases with sufficient tissue for analysis: 8 were men, 7 were stage I, 7 had adenocarcinoma, 8 had squamous cell carcinoma, 8 were former smokers, 7 were current smokers, 9 were Caucasian, and 6 were African-American. A total of 75 tissue samples were analyzed with an average sample weight of 2.9 mg. With the lower limit of detection at 0.001 ug/g, the median concentrations in ug/g for Cd, As, Hg, and Pb in primary lung tumor were 0.058 (range undetectable [Not]-0.316), 0.019 (range Not-0.078), 0 (range Not-0.015), and 0 (range Not-0.026); respectively. In distant non-malignant lung samples, the median concentrations in ug/g for Cd, As, Hg, and Pb were 0.204 (range Not-2.500), 0.025 (range Not-0.070), 0 (range Not-0.012), and Not; respectively. There were no significant inter-case differences for the heavy metal concentrations in primary lung tumor and stage, histology, gender, and race. However, distant non-malignant lung samples had significantly higher Cd levels compared to primary lung tumor (p=0.013). Conclusion: Using ICP-MS, concentrations of Cd, As, Hg, and Pb could be measured in low quantities of FFPE tissue. Significantly higher Cd content was observed in distant non-malignant lung tissue compared to primary lung tumor. There appears to be higher levels of Cd and As than Hg and Pb in the lung tissues of current/former smokers with NSCLC. Analysis of lung tissues from clinically-matched non-cancer patients is warranted.