Six Sigma^® is a popular quality program that has been applied to clinical laboratory assays. Sigma is calculated as (TEa − bias)/CV and these sigma numbers are often claimed as a sole measure of quality based on medical requirements. But these sigma calculations do not account for all results. An additional set of wider limits must be added, such that all data are accounted for. This gives a minimum of three zones: zone A, where 95% of the data should be; zone C, where there should be no data; and zone B, where 5% of the data is allowed. An additional problem is that sigma calculations are often based on valid analytical data, meaning that pre-analytical and post-analytical errors are excluded. Also, samples that are flagged by the system and produce no results are, of course, excluded, but delayed results can cause patient harm. A better measure of assay quality can be provided by a failure mode effects analysis (FMEA), which attempts to assess the probability of failure and its severity for every possible failure mode. In this paper, an example of what is entailed is described for two failure modes and the overall process is outlined. The amount of effort required for a full FMEA is beyond virtually any clinical laboratory. Some compromises are suggested. Calculating sigma values, which have little meaning about patient harm, is not recommended.