The detection, identification, and quantitation of transcripts have evolved from simple Northern analysis, cDNA cloning, and sequencing to RT-PCR, microarrays, and now digital gene expression using ultra-high-throughput RNA sequencing (RNA-Seq). During the course of our studies we observed that some microarray probes show very high signal intensity values yet are discordant when compared with RNA-Seq. A total of 99 probes from approximately 30,000 were identified as consistently discordant in four human tissues or cell lines. Interestingly, this set of discordant probes appears array-dependent. Among the 99 probes identified, 70 constantly exhibited a high signal in all 713 available samples surveyed using the Illumina HumanHT-12v4 platform. Some were discordant with additional probes that annotated the same genes. Absence of a number of these transcripts was confirmed by quantitative RT-PCR (qRT-PCR). Our findings suggest that one must be cautious, as some array probes do not capture the level of the target.