A gene expression profile analysis using an Affymetrix HG-U133 Plus 2.0 microarray with probes for 38,500 human full-length cDNAs was performed on a primary papillary thyroid carcinoma (PTC) and a nodular goiter (NG). ZCCHC12 was the gene with the most significant differential expression between PTC and NG, and this was verified using fluorescent quantitative PCR (FQ-PCR). A total of 9,485 genes were detected with a difference in transcription levels between PTC and NG. Of these, 2,098 were up-regulated with a signal log ratio (SLR) ≥ 1 and 1,714 were down-regulated with an SLR ≤ -1. Among these up-regulated and down-regulated genes, 12 genes were significantly up-regulated (SLR ≥ 5.0) and 6 genes were significantly down-regulated (SLR ≤ -5.0). The SLR of the ZCCHC12 gene was 8.8. The results of FQ-PCR showed that the medians of the log (ZCCHC12 RNA/GAPDH RNA) in PTC and NG were 0.73 and -1.68, respectively, and the difference between them was significant (P < 0.05). There were no significant correlations between the RNA levels of the ZCCHC12 gene and the clinicopathological and biochemical parameters of PTC in our pilot study. This study showed that a number of differentially expressed genes were discovered between PTC and NG. Significantly, the number of transcript copies of the ZCCHC12 gene in PTC was higher than in NG. The verified results of FQ-PCR were consistent with the microarray screening results. The ZCCHC12 gene may be a novel diagnostic molecular marker of PTC.