The process of disease diagnosis reminds of the process of solving a crime. This starts with a so-called ‘crime scene investigation’ (CSI) carried out in a highly systematic manner. The CSI is followed by ‘forensic investigation’ in specialized laboratories. The final step in solving a crime is the ‘crime scene reconstruction’ process, which involves systematic elimination of unlikely scenarios and comparison of results from the analysis of physical evidence with eye witness accounts. If more evidence becomes available, an ‘old case may be reactivated’. In this review, the same sequence of activities is followed to solve a plant disease problem using a case study of a disease that was difficult to diagnose, namely the ‘case’ of corky root of lettuce.