Rare cancers, affecting 1 in 5 cancer patients, disproportionally contribute to cancer mortality. This research focuses on liposarcoma, an understudied rare cancer with unknown risk factors and limited treatment options. Liposarcoma incident cases were identified from the U.S. Surveillance, Epidemiology, and End Result (SEER) program and the combined SEER-National Program of Cancer Registries (CNPCR) between 2001-2016. Incidence rates (age-adjusted and age-specific), 5-year survival, and the time trends were determined using SEER*stat software. Three-dimensional visualization of age-time curves was conducted for males and females. SEER liposarcoma cases represented~30% (n = 11,162) of the nationwide pool (N = 37,499). Both sources of data showed males accounting for~60% of the cases; 82%-86% cases were identified among whites. Age-adjusted incidence was greater among males vs. females and whites vs. blacks, whereas survival did not differ by sex and race. The dedifferentiated (57.2%), pleomorphic (64.1%), and retroperitoneal (63.9%) tumors had the worse survival. Nationwide, liposarcoma rates increased by 19%, with the annual percent increase (APC) of 1.43% (95% confidence interval (CI): 1.12-1.74). The APC was greater for males vs. females (1.67% vs. 0.89%) and retroperitoneal vs. extremity tumors (1.94% vs. 0.58%). Thus, incidence increased faster in the high-risk subgroup (males), and for retroperitoneal tumors, the low-survival subtype. The SEER generally over-estimated the rates and time trends compared to nationwide data but under-estimated time trends for retroperitoneal tumors. The time trends suggest an interaction between genetic and non-genetic modifiable risk factors may play a role in the etiology of this malignancy. Differences between SEER and CNCPR findings emphasize the need for nationwide cancer surveillance.have a considerable impact on the overall cancer outcomes. Limited treatment options, high costs of existing treatments, and frequent misdiagnosis of rare cancers burden patients, physicians, and health systems [4]. The lack of epidemiological knowledge about the risk factors associated with many rare cancers precludes the development of viable prevention, making it one of the most dramatic unresolved public health problems [1,3,5]. In comparison, well-studied cancers such as colorectal cancer, which constitutes a smaller portion of the overall cancer cases (13%), has had significant progress in cancer control and prevention [5,6]. The existing gaps in research and treatment are reflected in rare cancer survival rates. The 5-year survival for rare cancers is worse compared to common cancers: 49% vs. 63% in Europe [5]; and the U.S., 55% vs. 75% among males and 60% vs. 74% among females [4]. In light of these facts, population-based surveillance of rare cancers and their descriptive epidemiology provide the foundation for advancing etiological and clinical research with the ultimate goal of reducing the public health burden of rare cancers.This research focuses on the under-studied rare cancer...