Introduction: The Portuguese healthcare system had to adapt at short notice to the COVID-19 pandemic. We implemented workflow changes to our molecular pathology laboratory, a national reference center, to maximize safety and productivity. We assess the impact this situation had on our caseload and what conclusions can be drawn about the wider impact of the pandemic in oncological therapy in Portugal. Material and Methods. We reviewed our database for all oncological molecular tests requested between March and April of 2019 and 2020. For each case, we recorded age, sex, region of the country, requesting institution, sample type, testing method, and turnaround time (TAT). A comparison between years was made. Results: The total number of tests decreased from 421 in 2019 to 319 in 2020 (p = 0.0027). The greatest reduction was in clinical trial-related cases. Routine cases were similar between years (267 vs. 256). TAT was higher in 2019 (mean 15 days vs. 12.3 days; p = 0.0003). Medium- to large-sized public hospitals in the north of the country were mostly responsible for the reduction in cases (p = 0.0153). Conclusions: Case reduction was observed at hospitals that have mostly been involved in the treatment of COVID-19 and in the north of the country, the region worst-hit by the pandemic. Similar to other studies, our TAT decreased, even with a similar number of routine cases. Thus, we conclude that it is possible to successfully adapt the workflow of a molecular pathology laboratory to new safety standards without losing efficiency.