Rectal cancer (RC) appears to behave differently compared with colon cancer. We aimed to analyze existence of different subtypes of RC depending on distinct features (age of onset and the presence of synchronous primary malignant neoplasms). We compared the clinicopathological, familial and molecular features of three different populations diagnosed with RC (early-onset RC [EORC], late-onset RC, and synchronous RC [SRC]). Eighty-five RCs were identified and were evaluated according to their microsatellite instability, CpG Island Methylator Phenotype (CIMP) and chromosomal instability, as assessed by Next Generation Sequencing and microarray-based comparative genomic hybridization approaches. The results were subjected to cluster analysis. SRCs displayed the most specific characteristics including a trend for the development of multiple malignant neoplasms, a greater proportion of CIMP-High tumors (75%) and more frequent genomic alterations. These findings were confirmed by a clustering analysis that stratified RCs according to their genomic alterations. We also found that EORCs exhibited their own features including an important familial cancer component and a remarkable rate of mutations in TP53 (53%). Together, heterogeneity in RC characteristics by age of disease-onset and SRC warrants further study to optimize tailored prevention, detection and intervention strategies-particularly among young adults.