'monoclonal' originates from Greek and English elements: Greek 'mono-' meaning 'single' and Greek 'klōn' (via English 'clone') meaning 'twig' or 'sprout', combined with the English adjectival suffix '-al'.

'monoclonal' was formed in English by combining 'mono-' + 'clonal' (itself derived from 'clone', a 20th-century English coinage from Greek 'klōn'). The specific biomedical sense became prominent after the mid-20th century, especially following the development of monoclonal antibody technology in the 1970s.

Initially the components meant 'single' (mono-) and 'twig/sprout' (klōn), and the combined term came to mean 'relating to a single clone'; its modern usage has been specialized in biology and medicine (e.g., 'monoclonal antibody').