Objective: Fine needle aspiration (FNA) is a procedure used in the diagnosis of thyroid nodules. A definitive diagnosis is not possible when FNA shows follicular cells, and therefore a surgical intervention is necessary. Identifying genetic expression patterns in FNA samples of indeterminate thyroid nodules could assist in distinguishing benign from malignant follicular thyroid lesions. Methods: Patients with follicular cells on FNA and a pathologic diagnosis of either follicular thyroid adenoma (FTA) or carcinoma (FTC) were included. Thyroid tissue was collected at the time of definitive surgery. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used with an array profiler including 84 genes involved in transformation and tumorigenesis. RT2 Profiler PCR array data analysis software identified fold-change based upon ΔΔCt calculations. Gene expression was normalized to five housekeeping genes. Results: Nineteen patients were included: 10 with FTA and 9 with FTC on post-operative pathology. In the FTC group, 11 genes had greater than 2-fold up or down-regulation relative to the adenoma group; and two genes reached statistical significance, caspase-8 and IL-8 (p ≤ 0.05). Utilizing the Sub-Network Enrichment Analysis (SNEA) algorithm, sub-networks of genes involving the transforming growth factor (TGF) family and peroxisome proliferator-activated receptor delta (PPARδ) family were both highly regulated. Conclusions: Our preliminary data identify two potential genes that may aid in differentiating FTC from FTA, and demonstrates a potential role for qRT-PCR of FNA samples. This may contribute to the workup of thyroid nodules to ultimately guide the treatment of indeterminate follicular lesions.