The spleen is only uncommonly investigated in the forensic setting. Thorough examinations are performed in some specific situations such as splenic trauma (including iatrogenic trauma from cardiopulmonary resuscitation attempts), anaphylaxis, drowning, and sepsis-related deaths. The aim of this review is to present the available literature focusing on a few selected splenic diseases as well as forensic investigations performed on the spleen in order to summarize the most frequent situations in which this routinely unexplored organ may merit more extensive examination.