Surgery is now an option in the treatment of macular holes. However, their clinical features may be subtle and many conditions may masquerade as full-thickness macular holes. To promote diagnostic accuracy and thereby avoid incorrect or unnecessary surgery, we present several cases of entities misdiagnosed as full-thickness macular holes in an effort to determine which clinical features likely led to the inaccurate diagnosis. Among these were epiretinal membranes with pseudoholes, impending macular holes, lamellar macular holes, and macular degeneration. Important features allowing for a more certain diagnosis included: fine, drusen-like yellowish deposits in the base of the hole; a surrounding cuff of subretinal fluid; a distinct and circular margin around the hole; and an overlying operculum. Also, visual acuity was often relatively good in non-macular hole cases, while with true macular holes, vision is usually 20/80 or worse, or deteriorates to this level over a few weeks. Many entities falsely diagnosed as macular holes have a favorable natural history, are not amenable to surgical efforts, or require slightly different surgical maneuvers. Misdiagnosis and wrongful treatment may be minimized by limiting macular hole surgery to cases in which visual acuity is 20/80 or worse or by waiting for clinical changes sufficient to permit distinguishing false from early or atypical true cases.