Next-generation sequencing (NGS) has greatly reduced the cost of genetic testing. As a result, more cancer patients now have access to testing and this has improved clinical care. Nevertheless, the technology is still evolving and so are the applications and uptake of NGS testing in various settings. As with any new technology, there is a steep learning curve for both, the laboratory and the clinical services that use the results of testing. This talk will present a number of clinical cases that illustrate the power and limitations of NGS testing for cancer patients. Using clinical case studies, we will discuss mosaicism, ethnicity and variants of uncertain clinical significance, virtual gene panels and their design. We will give examples of why a genetic test result can be different from what was expected and how testing may change practise.