The hemophagocytic syndrome is a serious complication of several systemic illnesses. To define the characteristics of the hemophagocytic syndrome at a pediatric specialty hospital in Tuxtla Gutiérrez, Chiapas, Mexico; incidences, underdiagnosis and overdiagnosis, associated conditions, treatment, and prognosis were included. 214 cases of probable hemophagocytic syndrome that were seen between January 2011 and May 2019 were analyzed. 26 patients diagnosed with hemophagocytic syndrome and 188 cases with suspicion of this entity and/or ferritin > 500 ug/L were included. The cases that met four or more criteria of the HFS (Histiocyte Society, 2004) were included in this study. Thirty-five cases were validated (fourteen were previously diagnosed, nine had suspicion, and twelve had ferritin > 500 μg/L). Neither twelve out of 26 of the cases that were previously diagnosed (46.2 % overdiagnosed). Of the 35 validated cases, 21 hadn’t been diagnosed (60 % underdiagnosed) met the diagnostic criteria of the HFS. The annual occurrence was of 2.0/1000 egresses. The Epstein-Barr virus was involved in 42 % of the cases. The overall mortality was of 80 %. Hemophagocytic syndrome had been significantly underdiagnosed and overdiagnosed at the analyzed hospital. The clinical features allow early suspicion, diagnosis, and treatment. Specific and non-specific illnesses that were associated to hemophagocytic syndrome were identified.