Background: Worldwide, the incidence of cancers is increasing and is becoming a major public health issue, including those in the Asia Pacific region. South-East Asia is a region with diverse populations with different disease spectra. This study looked at the spectrum of cancers among South-East Asians working in Brunei Darussalam. Materials and Methods: The cancer registry from 1994 to 2012 maintained by the State Laboratory was retrospectively reviewed. Crude incidence rates were calculated based on the population census of 2010. Results: Altogether, there was a total of 418 cancer cases diagnosed among South-East Asians, giving an incidence of 5.1% (n=418/8,253). The affected nationals in decreasing frequency were Malaysians (53.1%), followed by Filipinos (25.8%), Indonesians (15.3%), Thais (3.8%), Myanmese (1.7%) and Vietnamese (0.2%) with no recorded cases for Singapore and the People’s Republic of Laos. The overall mean age of diagnosis was 46.1±4.2 years old, with an increasing trend over the years (p<0.05 ANOVA). The overall gender ratio was 42.3:57.7 (male:female), more females among the Filipinos and Indonesians, more males among the Thais, and equal representation among the Malaysians and the Myanmese. The most common were cancers of the digestive system (19.9%), followed by female reproductive/gynecologic system (16.0%), breast (15.6%), hematological/lymphatic (12.0%) and head/neck (8.1%). There were differences in the prevalence of cancers among the various nationalities with highest crude incidence rate among the Myanmese (141.2/100,000), followed by the Malaysian (88.5/100,000), and the Filipinos (40.6/100,000) and the lowest among the Thais (18.4/100,000), Indonesians (10.5/100,000) and the Vietnamese (6.3/100,000). Conclusions: Cancers among South-East Asian residing in Brunei Darussalam accounted for 5.1% of all cancers. The most common cancers were cancers of the digestive, gynecologic/female reproductive system and breast with certain types slowly increasing in proportions. There mean age of diagnoses was increasing.