Occupational asthma (OA) should be suspected in a worker with newly developed asthma exposed to agent known to cause asthma. First approach to diagnosis of OA is to obtain careful occupational history and seek possible agents at workplace. Published lists and databases of agents and workplaces are currently available. However some of them, TDI in furniture and musical instruments factories, reactive dyes in dye manufactories, and drugs in pharmaceutical workers and dust in highly dusty workplace, represent most case of OA. Therefore many physicians mechanically trace particular agent as cause of OA at such workplaces. Here we report 4 cases of OA caused by unusual agents in workers exposed to highly asthmogenic agents at workplace; formaldehyde at musical instruments factory, chromium at reactive dye manufactory, and TDI at dry powder painting work. In these cases, the diagnosis of OA was possible from multidisciplinary approaches; component analysis of chemicals, review of material safety-data sheet, and detail understanding of job duties and work processes. This study suggests that physician should look for unknown agent in highly suspicious case of OA with negative challenge test to agents known to develop asthma.