The collection contains approximately 1200 scores, chiefly for solo piano but also including other vocal and instrumental combinations. More than half the collection consists of photocopied scores, and there are more than 550 manuscripts and holographs (original and photocopy).

The collection was initially processed and described by Matthew Sheehy in 1997. The current description is expanded both in terms of the level of detail provided, the range of dates represented in the collection (thus the disparity between the earliest date (1762) now stated in the collection versus the date of 1828 in the title of the collection), and also by the inclusion of additional works identified after the initial inventory was prepared. Also, some works in the series of unmarked scores are individually noted as having markings due to later examination. The major portion of the additions consists of works that Mikhashoff grouped together. They reflect some of his research interests and themes associated with concert programs he presented. These groupings include folders of material related to composers, including Lukas Foss's Solo for piano, composed for Mikhashoff, Charles Ives's Second piano sonata (Concord sonata), Sylvano Bussotti's Racine, pianobar pour Phèdre, a collection of works by Percy Grainger, and Virgil Thomson's series of musical portraits. Thematic programs include the concerts titled The Golden Clavier, Hollywood elegies, Miss Jane's parlor, Opera matinee, and From Vienna to New York. There are also groupings for the works Mikhashoff collected for his Melodeclamation concerts and for the Buffalo Piano Collection that he compiled.

The range of repertoire, chiefly from the 19th and 20th centuries, is impressively broad. While Mikhashoff was best known for his performances of contemporary music, his research uncovered many works of the piano repertoire from many lesser-known composers, some of whom are now forgotten or rarely performed. The list of composers included in the collection is indicative of Mikhashoff's involvement in contemporary music in America and internationally.

More than half of the scores contain annotations made by Mikhashoff in preparation for performance. The markings represent Mikhashoff's entire career: from markings on piano exercises such as Czerny's School of velocity, marked for Mikhashoff's piano lessons at age fourteen in 1955, through works composed for him during his last year of life. Many scores bear only incidental markings but there are also scores that are extensively marked. Mikhashoff sometimes re-notated works or passages from works, usually to make them more legible. Mikhashoff's versions of Foss's Solo for piano and Virgil Thomson's Nineteen portraits for piano were used for the published versions of those works.