In ancient Greece there were three standard tunings (known by the Latin word genus, plural genera) of a lyre. These three tunings were called diatonic, chromatic, and enharmonic, and the sequences of four notes that they produced were called tetrachords ("four strings"). A diatonic tetrachord comprised, in descending order, two whole tones and a semitone, such as A G F E (roughly). In the chromatic tetrachord the second string of the lyre was lowered from G to G♭, so that the two lower intervals in the tetrachord were semitones, making the pitches A G♭ F E. In the enharmonic tetrachord the tuning had two quarter tone intervals at the bottom: A G F E (where F is F♮ lowered by a quarter tone). For all three tetrachords, only the middle two strings varied in their pitch.
The term cromatico (Italian) was occasionally used in the Medieval and Renaissance periods to refer to the coloration (Latin coloratio) of certain notes. The details vary widely by period and place, but generally the addition of a colour (often red) to an empty or filled head of a note, or the "colouring in" of an otherwise empty head of a note, shortens the duration of the note. In works of the Ars Nova from the 14th century, this was used to indicate a temporary change in metre from triple to duple, or vice versa. This usage became less common in the 15th century as open white noteheads became the standard notational form for minims (half-notes) and longer notes called white mensural notation. Similarly, in the 16th century, a form of notating secular music, especially madrigals in was referred to as "chromatic" because of its abundance of "coloured in" black notes, that is semiminims (crotchets or quarter notes) and shorter notes, as opposed to the open white notes in , commonly used for the notation of sacred music. These uses for the word have no relationship to the modern meaning of chromatic, but the sense survives in the current term coloratura.
The term chromatic began to approach its modern usage in the 16th century. For instance Orlando Lasso's Prophetiae Sibyllarum opens with a prologue proclaiming, "these chromatic songs, heard in modulation, are those in which the mysteries of the Sibyls are sung, intrepidly," which here takes its modern meaning referring to the frequent change of key and use of chromatic intervals in the work. (The Prophetiae belonged to an experimental musical movement of the time, called musica reservata). This usage comes from a renewed interest in the Greek genera, especially its chromatic tetrachord, notably by the influential theorist Nicola Vicentino in his treatise on ancient and modern practice, 1555.