A correctly implemented and widely accepted vaccination campaign was the only truly effective weapon to reduce mortality and hospitalizations related to COVID-19. However, it was not 100% effective and has not eliminated COVID-19. Even though more than 60% of the worldwide population is fully vaccinated (meaning that these subjects have completed the recommended vaccine cycle), subjects continue to die from COVID-19, particularly in the presence of comorbidities. In this scenario, autopsies play a crucial role in understanding the pathophysiological mechanisms of SARS-CoV-2 in vaccinated subjects and adapting therapies accordingly. This case report analyzes the death of a fully vaccinated patient who suffered from comorbidities and died from COVID-19; we provide a complete autopsy data set. On microscopic examination, the lungs showed massive interstitial pneumonia, areas of inflammation with interstitial lympho-plasma cell infiltrate, and interstitial edema. The liver showed granulocytes within the hepatic parenchyma. All these elements were consistent with previous published data on unvaccinated patients who had died from COVID-19. The present study is the first that analyzes, through a complete autopsy and a microscopic analysis of all organs, a death related to COVID-19 despite vaccine administration. In this regard, to the best of our knowledge, no other studies have been published reporting a complete autopsy. This study reports, on the one hand, the importance of vaccination programs in the fight against COVID-19, and, on the other hand, it hypothesizes that the vaccine does not offer complete immunity to SARS-CoV-2, particularly in elderly subjects with comorbidities.