Extra-chromosomal DNA (ecDNA) is a genetic error found in more than 30% of tumour samples across various cancer types. It is a key driver of oncogene amplification promoting tumour progression and therapeutic resistance, and is correlated to the worse clinical outcomes. Different from chromosomal DNA where genetic materials are on average equally divided to daughter cells controlled by centromeres during mitosis, the segregation of ecDNA copies is random partition and leads to a fast accumulation of cell-to-cell heterogeneity in copy numbers.  I will present our analytical and computational modeling of ecDNA dynamics under random segregation, examining the impact of copy-number-dependent versus -independent fitness, as well as the maintenance and de-mixing of multiple ecDNA species or variants within single cells. By integrating experimental and clinical data, our results demonstrate that ecDNA is not merely a by-product but a driving force in tumor progression. Intra-tumor heterogeneity exists not only in copy number but also in genetic and phenotypic diversity. Furthermore, ecDNA fitness can be copy-number dependent, which has significant implications for treatment.