Specimen of a spleen is most frequently encountered in centers that deal with autopsy cases. Spleen is not a frequent surgically resected specimen thereby indicating its uncommon presentation with a primary disorder. Most pathologists tend to have a casual approach or consider spleen to be an organ with a difficult or a non-specific morphology. Understanding and interpreting splenic pathology remain a challenge for a pathologist. There are only few diseases which primarily involve the spleen and represent involvement by diseases originating elsewhere. The contribution of a histopathologist in such situation is in confirmation of the clinical diagnosis or exclusion of a suspected pathology. Splenic pathology is of a combined interest to a surgeon, hematologist, histopathologist and an oncologist. There are certain prerequisites for a proper interpretation of splenic pathology like availability of an adequate clinical history, lab investigation, systematic gross examination and studying of sections from a properly fixed specimen. A freshly removed specimen of spleen needs to be thoroughly examined after removal of the attached fat, lymph nodes; splenicule if any and other undesired adherent tissue on the capsule and the hilum. Vessels at hilum are left with adequate length for examination and detail study if need be. After cleaning, the spleen is weighed and measured. The specimen is cut with a sharp knife at an interval of 5 mm thickness along the length exposing the hilum. Any excess blood is shocked with a clean towel and smears can be made. Alternatively, excess blood can be cleaned by washing gently under running tap water. The cut slices are put into fixative and left overnight for fixation. The smears can either be fixed immediately with absolute alcohol or left to dry in the air. Representative sampling can be done immediately in the fresh state or after overnight fixation. Number of blocks to be sampled will depend on the size and gross feature of the specimen. Minimum of two blocks is usually sampled from different area of the spleen including the hilum and capsule.